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  • 1.
    Abdellah, Tebani
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Gummesson, Anders
    Zhong, Wen
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Koistinen, Ina Schuppe
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lakshmikanth, Tadepally
    Olsson, Lisa M.
    Boulund, Fredrik
    Neiman, Maja
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Stenlund, Hans
    Hellström, Cecilia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Karlsson, Max
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Arif, Muhammad
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Dodig-Crnkovic, Tea
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mardinoglu, Adil
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London, England.
    Lee, Sunjae
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Zhang, Cheng
    Chen, Yang
    Olin, Axel
    Mikes, Jaromir
    Danielsson, Hanna
    von Feilitzen, Kalle
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Jansson, Per-Anders
    Angerås, Oskar
    Huss, Mikael
    Kjellqvist, Sanela
    Odeberg, Jacob
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Edfors, Fredrik
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Tremaroli, Valentina
    Forsström, Björn
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Schwenk, Jochen M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Moritz, Thomas
    Bäckhed, Fredrik
    Engstrand, Lars
    Brodin, Petter
    Bergström, Göran
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. Danish Tech Univ, Ctr Biosustainabil, Copenhagen, Denmark.
    Fagerberg, Linn
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Integration of molecular profiles in a longitudinal wellness profiling cohort2020Ingår i: Nature Communications, E-ISSN 2041-1723, Vol. 11, nr 1, artikel-id 4487Artikel i tidskrift (Refereegranskat)
  • 2.
    Ahmadian, Afshin
    et al.
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Russom, Aman
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Andersson, Helene
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Uhlén, Mathias
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Stemme, Göran
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Nilsson, Peter
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    SNP analysis by allele-specific extension in a micromachined filter chamber2002Ingår i: BioTechniques, ISSN 0736-6205, E-ISSN 1940-9818, Vol. 32, nr 4, s. 748-754Artikel i tidskrift (Refereegranskat)
  • 3.
    Alkharaan, Hassan
    et al.
    Karolinska Inst, Dept Dent Med, Alfred Nobels Alle 8, S-14104 Stockholm, Sweden..
    Bayati, Shaghayegh
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hellström, Cecilia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Aleman, Soo
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Olsson, Annika
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden..
    Lindahl, Karin
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Bogdanovic, Gordana
    Karolinska Univ Hosp, Dept Clin Microbiol, Stockholm, Sweden..
    Healy, Katie
    Karolinska Inst, Dept Dent Med, Alfred Nobels Alle 8, S-14104 Stockholm, Sweden..
    Tsilingaridis, Georgios
    Karolinska Inst, Dept Dent Med, Alfred Nobels Alle 8, S-14104 Stockholm, Sweden..
    De Palma, Patricia
    Karolinska Inst, Dept Dent Med, Alfred Nobels Alle 8, S-14104 Stockholm, Sweden..
    Hober, Sophia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Månberg, Anna
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Pin, Elisa
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Chen, Margaret Sallberg
    Karolinska Inst, Dept Dent Med, Alfred Nobels Alle 8, S-14104 Stockholm, Sweden..
    Persisting Salivary IgG Against SARS-CoV-2 at 9 Months After Mild COVID-19: A Complementary Approach to Population Surveys2021Ingår i: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 224, nr 3, s. 407-414Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Declining humoral immunity in coronavirus disease 2019 (COVID-19) patients and possible reinfection have raised concern. Mucosal immunity, particularly salivary antibodies, may be short lived although long-term studies are lacking. Methods. Using a multiplex bead-based array platform, we investigated antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins in 256 saliva samples from convalescent patients 1-9 months after symptomatic COVID-19 (n = 74, cohort 1), undiagnosed individuals with self-reported questionnaires (n = 147, cohort 2), and individuals sampled prepandemic (n = 35, cohort 3). Results. Salivary IgG antibody responses in cohort 1 (mainly mild COVID-19) were detectable up to 9 months postrecovery, with high correlations between spike and nucleocapsid specificity. At 9 months, IgG remained in blood and saliva in most patients. Salivary IgA was rarely detected at this time point. In cohort 2, salivary IgG and IgA responses were significantly associated with recent history of COVID-19-like symptoms. Salivary IgG tolerated temperature and detergent pretreatments. Conclusions. Unlike SARS-CoV-2 salivary IgA that appeared short lived, specific saliva IgG appeared stable even after mild COVID-19, as for blood serology. This noninvasive saliva-based SARS-CoV-2 antibody test with home self-collection may be a complementary alternative to conventional blood serology.

  • 4.
    Andersson, Anders
    et al.
    KTH, Skolan för bioteknologi (BIO).
    Bernander, R.
    Department of Molecular Evolution, Evolutionary Biology Center, Uppsala University.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO).
    Dual-genome primer design for construction of DNA microarrays2005Ingår i: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 21, nr 3, s. 325-332Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Motivation: Microarray experiments using probes covering a whole transcriptome are expensive to initiate, and a major part of the costs derives from synthesizing gene-specific PCR primers or hybridization probes. The high costs may force researchers to limit their studies to a single organism, although comparing gene expression in different species would yield valuable information. Results: We have developed a method, implemented in the software DualPrime, that reduces the number of primers required to amplify the genes of two different genomes. The software identifies regions of high sequence similarity, and from these regions selects PCR primers shared between the genomes, such that either one or, preferentially, both primers in a given PCR can be used for amplification from both genomes. To assure high microarray probe specificity, the software selects primer pairs that generate products of low sequence similarity to other genes within the same genome. We used the software to design PCR primers for 2182 and 1960 genes from the hyperthermophilic archaea Sulfolobus solfataricus and Sulfolobus acidocaldarius, respectively. Primer pairs were shared among 705 pairs of genes, and single primers were shared among 1184 pairs of genes, resulting in a saving of 31% compared to using only unique primers. We also present an alternative primer design method, in which each gene shares primers with two different genes of the other genome, enabling further savings.

  • 5.
    Andersson, Anders
    et al.
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Keskitalo, J.
    Sjödin, A.
    Bhalerao, Rupali
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Sterky, Fredrik
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Wissel, K.
    Tandre, K.
    Aspeborg, Henrik
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Moyle, R.
    Ohmiya, Y.
    Brunner, A.
    Gustafsson, P.
    Karlsson, J.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Nilsson, O.
    Sandberg, G.
    Strauss, S.
    Sundberg, B.
    Uhlén, Mathias
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Jansson, S.
    Nilsson, Peter
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    A transcriptional timetable of autumn senescence2004Ingår i: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 5, nr 4, s. R24-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: We have developed genomic tools to allow the genus Populus ( aspens and cottonwoods) to be exploited as a full-featured model for investigating fundamental aspects of tree biology. We have undertaken large-scale expressed sequence tag ( EST) sequencing programs and created Populus microarrays with significant gene coverage. One of the important aspects of plant biology that cannot be studied in annual plants is the gene activity involved in the induction of autumn leaf senescence. Results: On the basis of 36,354 Populus ESTs, obtained from seven cDNA libraries, we have created a DNA microarray consisting of 13,490 clones, spotted in duplicate. Of these clones, 12,376 (92%) were confirmed by resequencing and all sequences were annotated and functionally classified. Here we have used the microarray to study transcript abundance in leaves of a free-growing aspen tree ( Populus tremula) in northern Sweden during natural autumn senescence. Of the 13,490 spotted clones, 3,792 represented genes with significant expression in all leaf samples from the seven studied dates. Conclusions: We observed a major shift in gene expression, coinciding with massive chlorophyll degradation, that reflected a shift from photosynthetic competence to energy generation by mitochondrial respiration, oxidation of fatty acids and nutrient mobilization. Autumn senescence had much in common with senescence in annual plants; for example many proteases were induced. We also found evidence for increased transcriptional activity before the appearance of visible signs of senescence, presumably preparing the leaf for degradation of its components.

  • 6.
    Andersson, Anders
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Lundgren, Magnus
    Department of Molecular Evolution, Evolutionary Biology Center, Uppsala University.
    Eriksson, Stefan
    Department of Molecular Evolution, Evolutionary Biology Center, Uppsala University.
    Rosenlund, Magnus
    KTH, Skolan för teknikvetenskap (SCI), Matematik (Inst.).
    Bernander, Rolf
    Department of Molecular Evolution, Evolutionary Biology Center, Uppsala University.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Global analysis of mRNA stability in the archaeon Sulfolobus2006Ingår i: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 7, nr 10, s. R99-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Transcript half-lives differ between organisms, and between groups of genes within the same organism. The mechanisms underlying these differences are not clear, nor are the biochemical properties that determine the stability of a transcript. To address these issues, genome-wide mRNA decay studies have been conducted in eukaryotes and bacteria. In contrast, relatively little is known about RNA stability in the third domain of life, Archaea. Here, we present a microarray-based analysis of mRNA half-lives in the hyperthermophilic crenarchaea Sulfolobus solfataricus and Sulfolobus acidocaldarius, constituting the first genome-wide study of RNA decay in archaea. Results: The two transcriptomes displayed similar half-life distributions, with medians of about five minutes. Growth-related genes, such as those involved in transcription, translation and energy production, were over-represented among unstable transcripts, whereas uncharacterized genes were over-represented among the most stable. Half-life was negatively correlated with transcript abundance and, unlike the situation in other organisms, also negatively correlated with transcript length. Conclusion: The mRNA half-life distribution of Sulfolobus species is similar to those of much faster growing bacteria, contrasting with the earlier observation that median mRNA half-life is proportional to the minimal length of the cell cycle. Instead, short half-lives may be a general feature of prokaryotic transcriptomes, possibly related to the absence of a nucleus and/or more limited post-transcriptional regulatory mechanisms. The pattern of growth-related transcripts being among the least stable in Sulfolobus may also indicate that the short half-lives reflect a necessity to rapidly reprogram gene expression upon sudden changes in environmental conditions.

  • 7.
    Andersson, Anders
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Pelve, Erik A.
    Lindeberg, Stefan
    Lundgren, Magnus
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Bernander, Rolf
    Replication-biased genome organisation in the crenarchaeon Sulfolobus2010Ingår i: BMC Genomics, E-ISSN 1471-2164, Vol. 11, s. 454-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Species of the crenarchaeon Sulfolobus harbour three replication origins in their single circular chromosome that are synchronously initiated during replication. Results: We demonstrate that global gene expression in two Sulfolobus species is highly biased, such that early replicating genome regions are more highly expressed at all three origins. The bias by far exceeds what would be anticipated by gene dosage effects alone. In addition, early replicating regions are denser in archaeal core genes (enriched in essential functions), display lower intergenic distances, and are devoid of mobile genetic elements. Conclusion: The strong replication-biased structuring of the Sulfolobus chromosome implies that the multiple replication origins serve purposes other than simply shortening the time required for replication. The higher-level chromosomal organisation could be of importance for minimizing the impact of DNA damage, and may also be linked to transcriptional regulation.

  • 8.
    Andersson, Annika
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Remnestål, Julia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nellgård, B.
    Vunk, Helian
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Kotol, David
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Edfors, Fredrik
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Schwenk, Jochen M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Ilag, L. L.
    Zetterberg, H.
    Blennow, K.
    Månberg, Anna
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Fredolini, Claudia
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Development of parallel reaction monitoring assays for cerebrospinal fluid proteins associated with Alzheimer's disease2019Ingår i: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 494, s. 79-93Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Detailed knowledge of protein changes in cerebrospinal fluid (CSF) across healthy and diseased individuals would provide a better understanding of the onset and progression of neurodegenerative disorders. In this study, we selected 20 brain-enriched proteins previously identified in CSF by antibody suspension bead arrays (SBA) to be potentially biomarkers for Alzheimer's disease (AD) and verified these using an orthogonal approach. We examined the same set of 94 CSF samples from patients affected by AD (including preclinical and prodromal), mild cognitive impairment (MCI), non-AD dementia and healthy individuals, which had previously been analyzed by SBA. Twenty-eight parallel reaction monitoring (PRM) assays were developed and 13 of them could be validated for protein quantification. Antibody profiles were verified by PRM. For seven proteins, the antibody profiles were highly correlated with the PRM results (r > 0.7) and GAP43, VCAM1 and PSAP were identified as potential markers of preclinical AD. In conclusion, we demonstrate the usefulness of targeted mass spectrometry as a tool for the orthogonal verification of antibody profiling data, suggesting that these complementary methods can be successfully applied for comprehensive exploration of CSF protein levels in neurodegenerative disorders.

  • 9.
    Andersson, Helene
    et al.
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    van der Wijngaart, Wouter
    KTH, Tidigare Institutioner (före 2005), Signaler, sensorer och system.
    Nilsson, Peter
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Enoksson, P.
    Stemme, Göran
    KTH, Tidigare Institutioner (före 2005), Signaler, sensorer och system.
    A valve-less diffuser micropump for microfluidic analytical systems2001Ingår i: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 72, nr 3, s. 259-265Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The suitability of valve-less micropumps in biochemistry has been shown. Fluids encountered in various biochemical methods that are problematic for other micropumps have been pumped with good performance. The pump is fabricated as a silicon-glass stack with a new process involving three subsequent deep reactive ion etching steps. Some of the main advantages of the valve-less diffuser pump are the absence of moving parts (excluding the pump diaphragm), the uncomplicated planar design, and high pump performance in terms of pressure head and flow rare. In addition, the micropump is self-priming and insensitive to particles and bubbles present in the pumped media. The results show that the valve-less micropump successfully pumps fluids within the viscosity range of 0.001-0.9 N s/m(2). The micropump is not sensitive to the density, ionic strength, or pH of the pumped media. Effective pumping of solutions containing beads of different sizes was also demonstrated. Living cells were pumped without inducing cell damage and no cell adhesion within the pump chamber was found. No valve-less micropump has previously been reported to pump such a wide variety of fluids.

  • 10. Andersson, T.
    et al.
    Unneberg, P.
    Nilsson, Peter
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Odeberg, Jacob
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Quackenbush, J.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Monitoring of representational difference analysis subtraction procedures by global microarrays2002Ingår i: BioTechniques, ISSN 0736-6205, E-ISSN 1940-9818, Vol. 32, nr 6, s. 1348-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Various approaches to the study of differential gene expression are applied to compare cell lines and tissue samples in a wide range of biological contexts. The compromise between focusing on only the important genes in certain cellular processes and achieving a complete picture is critical for the selection of strategy. We demonstrate how global microarray technology can be used for the exploration of the differentially expressed genes extracted through representational difference analysis (RDA). The subtraction of ubiquitous gene fragments from the two samples was demonstrated using cDNA microarrays including more than 32 000 spotted, PCR-amplified human clones. Hybridizations indicated the expression of 9100 of the microarray elements in a macrophage/foam cell atherosclerosis model system, of which many were removed during the RDA process. The stepwise subtraction procedure was demonstrated to yield an efficient enrichment of gene fragments overrepresented in either sample (18% in the representations, 86% after the first subtraction, and 88% after the second subtraction), many of which were impossible to detect in the starting material. Interestingly, the method allowed for the observation of the differential expression of several members of the low-abundant nuclear receptor gene family. We also observed a certain background level in the difference products of nondifferentially expressed gene fragments, warranting a verification strategy for selected candidate genes. The differential expression of several genes was verified by real-time PCR.

  • 11. Andersson-Gunneras, S.
    et al.
    Mellerowicz, E. J.
    Love, J.
    Segerman, B.
    Ohmiya, Y.
    Coutinho, P. M.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Henrissat, B.
    Moritz, T.
    Sundberg, B.
    Biosynthesis of cellulose-enriched tension wood in Populus: global analysis of transcripts and metabolites identifies biochemical and developmental regulators in secondary wall biosynthesis2006Ingår i: The Plant Journal, ISSN 0960-7412, E-ISSN 1365-313X, Vol. 45, nr 2, s. 144-165Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Stems and branches of angiosperm trees form tension wood (TW) when exposed to a gravitational stimulus. One of the main characteristics of TW, which distinguishes it from normal wood, is the formation of fibers with a thick inner gelatinous cell wall layer mainly composed of crystalline cellulose. Hence TW is enriched in cellulose, and deficient in lignin and hemicelluloses. An expressed sequence tag library made from TW-forming tissues in Populus tremula (L.) x tremuloides (Michx.) and data from transcript profiling using microarray and metabolite analysis were obtained during TW formation in Populus tremula (L.) in two growing seasons. The data were examined with the aim of identifying the genes responsible for the change in carbon

  • 12. Arabi, A.
    et al.
    Ullah, K.
    Branca, R. M. M.
    Johansson, J.
    Bandarra, D.
    Haneklaus, M.
    Fu, J.
    Ariës, I.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Den Boer, M. L.
    Pokrovskaja, K.
    Grandér, D.
    Xiao, G.
    Rocha, S.
    Lehtiö, J.
    Sangfelt, O.
    Proteomic screen reveals Fbw7 as a modulator of the NF-kappa B pathway2012Ingår i: Nature Communications, E-ISSN 2041-1723, Vol. 3, s. 976-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fbw7 is a ubiquitin-ligase that targets several oncoproteins for proteolysis, but the full range of Fbw7 substrates is not known. Here we show that by performing quantitative proteomics combined with degron motif searches, we effectively screened for a more complete set of Fbw7 targets. We identify 89 putative Fbw7 substrates, including several disease-associated proteins. The transcription factor NF-κB2 (p100/p52) is one of the candidate Fbw7 substrates. We show that Fbw7 interacts with p100 via a conserved degron and that it promotes degradation of p100 in a GSK3 2 phosphorylation-dependent manner. Fbw7 inactivation increases p100 levels, which in the presence of NF-κB pathway stimuli, leads to increased p52 levels and activity. Accordingly, the apoptotic threshold can be increased by loss of Fbw7 in a p100-dependent manner. In conclusion, Fbw7-mediated destruction of p100 is a regulatory component restricting the response to NF-κB2 pathway stimulation.

  • 13. Arner, P.
    et al.
    Henjes, Frauke
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Darmanis, Spyros N.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Dahlman, I.
    Iresjö, B. -M
    Naredi, P.
    Agustsson, T.
    Lundholm, K.
    Nilsson, Peter M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Rydén, M.
    Circulating Carnosine Dipeptidase 1 associates with weight loss and poor prognosis in gastrointestinal cancer2015Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 10, nr 4, artikel-id e0123566Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Cancer cachexia (CC) is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia. Design/Subjects: Plasma was obtained from a screening cohort of 59 patients, newly diagnosed with suspected gastrointestinal cancer, with (n = 32) or without (n = 27) cachexia. Samples were subjected to proteomic profiling using 760 antibodies (targeting 698 individual proteins) from the Human Protein Atlas project. The main findings were validated in a cohort of 93 patients with verified and advanced pancreas cancer. Results: Only six proteins displayed differential plasma levels in the screening cohort. Among these, Carnosine Dipeptidase 1 (CNDP1) was confirmed by sandwich immunoassay to be lower in CC (p = 0.008). In both cohorts, low CNDP1 levels were associated with markers of poor prognosis including weight loss, malnutrition, lipid breakdown, low circulating albumin/IGF1 levels and poor quality of life. Eleven of the subjects in the discovery cohort were finally diagnosed with non-malignant disease but omitting these subjects from the analyses did not have any major influence on the results. Conclusions: In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. These results, together with recently published data demonstrating lower circulating CNDP1 in subjects with glioblastoma and metastatic prostate cancer, suggest that CNDP1 may constitute a marker of aggressive cancer and CC.

  • 14.
    Aspeborg, Henrik
    et al.
    KTH, Skolan för bioteknologi (BIO).
    Schrader, J.
    Coutinho, P. M.
    Stam, M.
    Kallas, A.
    Djerbi, S.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Denman, S.
    Amini, B.
    Sterky, Fredrik
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Master, E.
    Sandberg, G.
    Mellerowicz, E.
    Sundberg, B.
    Henrissat, B.
    Teeri, Tuula T.
    KTH, Skolan för bioteknologi (BIO), Glykovetenskap.
    Carbohydrate-active enzymes involved in the secondary cell wall biogenesis in hybrid aspen2005Ingår i: Plant Physiology, ISSN 0032-0889, E-ISSN 1532-2548, Vol. 137, nr 3, s. 983-997Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Wood formation is a fundamental biological process with significant economic interest. While lignin biosynthesis is currently relatively well understood, the pathways leading to the synthesis of the key structural carbohydrates in wood fibers remain obscure. We have used a functional genomics approach to identify enzymes involved in carbohydrate biosynthesis and remodeling during xylem development in the hybrid aspen Populus tremula x tremuloides. Microarrays containing cDNA clones from different tissue-specific libraries were hybridized with probes obtained from narrow tissue sections prepared by cryosectioning of the developing xylem. Bioinformatic analyses using the sensitive tools developed for carbohydrate-active enzymes allowed the identification of 25 xylem-specific glycosyltransferases belonging to the Carbohydrate-Active EnZYme families GT2, GT8, GT14, GT31, GT43, GT47, and GT61 and nine glycosidases (or transglycosidases) belonging to the Carbohydrate-Active EnZYme families GH9, GH10, GH16, GH17, GH19, GH28, GH35, and GH51. While no genes encoding either polysaccharide lyases or carbohydrate esterases were found among the secondary wall-specific genes, one putative O-acetyltransferase was identified. These wood-specific enzyme genes constitute a valuable resource for future development of engineered fibers with improved performance in different applications.

  • 15. Asplund, A.
    et al.
    Bjorklund, M. Gry
    Sundquist, C.
    Stromberg, S.
    Edlund, K.
    Oestman, A.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Ponten, F.
    Lundeberg, Joakim
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Expression profiling of microdissected cell populations selected from basal cells in normal epidermis and basal cell carcinoma2008Ingår i: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 158, nr 3, s. 527-538Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Basal cell carcinomas (BCCs) are prevalent tumours with uniform histology that develop without any known precursor lesion. Alterations in the sonic hedgehog-patched1 signalling pathway are accepted as necessary events for tumorigenesis, and mutations in the patched1 gene are frequently present in tumours. Objectives To analyse transcript profiles in BCC. Methods We used laser-assisted microdissection to isolate and collect cell populations defined under the microscope. Peripheral cells from nests of BCC were selected to represent tumour cells, and normal keratinocytes from epidermis basal layer were used as control. Extracted RNA was amplified and hybridized on to a cDNA microarray. Results Our results show that BCC cells express a transcript signature that is significantly different from that of normal keratinocytes, and over 350 genes with various functions were identified as differentially expressed. The compiled data suggest an upregulation of the Wnt signalling pathway as a major event in BCC cells. Furthermore, tumour cells appear to have an increased sensitivity to oxygen radicals and dysregulated genes involved in antigen presentation. Results were validated at both the transcriptional level using real-time polymerase chain reaction and at the protein level using immunohistochemistry. Conclusions We show that microdissection in combination with robust strategies for RNA extraction, amplification and cDNA microarray analysis allow for reliable transcript profiling and that antibody-based proteomics provides an advantageous strategy for the analysis of corresponding differentially expressed proteins. We found that expression patterns were significantly altered in BCC cells compared with basal keratinocytes and that the Wnt signalling pathway was upregulated in tumour cells.

  • 16. Asplund Högelin, K.
    et al.
    Ruffin, N.
    Pin, Elisa
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hober, Sophia
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Starvaggi Cucuzza, C.
    Khademi, M.
    Olsson, T.
    Piehl, F.
    Al Nimer, F.
    B-cell repopulation dynamics and drug pharmacokinetics impact SARS-CoV-2 vaccine efficacy in anti-CD20-treated multiple sclerosis patients2022Ingår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 29, nr 11, s. 3317-3328Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and purpose: Recent findings document a blunted humoral response to SARS-CoV-2 vaccination in patients on anti-CD20 treatment. Although most patients develop a cellular response, it is still important to identify predictors of seroconversion to optimize vaccine responses. Methods: We determined antibody responses after SARS-CoV-2 vaccination in a real-world cohort of multiple sclerosis patients (n = 94) treated with anti-CD20, mainly rituximab, with variable treatment duration (median = 2.9, range = 0.4–9.6 years) and time from last anti-CD20 infusion to vaccination (median = 190, range = 60–1032 days). Results: We find that presence of B cells and/or rituximab in blood predict seroconversion better than time since last infusion. Using multiple logistic regression, presence of >0.5% B cells increased probability of seroconversion with an odds ratio (OR) of 5.0 (95% confidence interval [CI] = 1.0–28.1, p = 0.055), whereas the corresponding OR for ≥6 months since last infusion was 1.45 (95% CI = 0.20–10.15, p = 0.705). In contrast, detectable rituximab levels were negatively associated with seroconversion (OR = 0.05, 95% CI = 0.002–0.392, p = 0.012). Furthermore, naïve and memory IgG+ B cells correlated with antibody levels. Although retreatment with rituximab at 4 weeks or more after booster depleted spike-specific B cells, it did not noticeably affect the rate of decline in antibody titers. Interferon-γ and/or interleukin-13 T-cell responses to the spike S1 domain were observed in most patients, but with no correlation to spike antibody levels. Conclusions: These findings are relevant for providing individualized guidance to patients and planning of vaccination schemes, in turn optimizing benefit–risk with anti-CD20. 

  • 17.
    Ayoglu, Burcu
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Birgersson, Elin
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mezger, Anja
    Nilsson, Mats
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Multiplexed protein profiling by sequential affinity capture2016Ingår i: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 16, nr 8, s. 1251-1256Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Antibody microarrays enable parallelized and miniaturized analysis of clinical samples, and have proven to provide novel insights for the analysis of different proteomes. However, there are concerns that the performance of such direct labeling and single antibody assays are prone to off-target binding due to the sample context. To improve selectivity and sensitivity while maintaining the possibility to conduct multiplexed protein profiling, we developed a multiplexed and semi-automated sequential capture assay. This novel bead-based procedure encompasses a first antigen capture, labeling of captured protein targets on magnetic particles, combinatorial target elution and a read-out by a secondary capture bead array. We demonstrate in a proof-of-concept setting that target detection via two sequential affinity interactions reduced off-target contribution, while lowered background and noise levels, improved correlation to clinical values compared to single binder assays. We also compared sensitivity levels with single binder and classical sandwich assays, explored the possibility for DNA-based signal amplification, and demonstrate the applicability of the dual capture bead-based antibody microarray for biomarker analysis. Hence, the described concept enhances the possibilities for antibody array assays to be utilized for protein profiling in body fluids and beyond.

  • 18.
    Ayoglu, Burcu
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Chaouch, Amina
    Lochmüller, Hanns
    Politano, Luisa
    Bertini, Enrico
    Spitali, Pietro
    Hiller, Monika
    Niks, Eric H.
    Gualandi, Francesca
    Pontén, Fredrik
    Bushby, Kate
    Aartsma-Rus, Annemieke
    Schwartz, Elena
    Le Priol, Yannick
    Straub, Volker
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Cirak, Sebahattin
    't Hoen, Peter A. C.
    Muntoni, Francesco
    Ferlini, Alessandra
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Szigyarto, Cristina Al-Khalili
    Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies2014Ingår i: EMBO Molecular Medicine, ISSN 1757-4676, E-ISSN 1757-4684, Vol. 6, nr 7, s. 918-936Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Despite the recent progress in the broad-scaled analysis of proteins in body fluids, there is still a lack in protein profiling approaches for biomarkers of rare diseases. Scarcity of samples is the main obstacle hindering attempts to apply discovery driven protein profiling in rare diseases. We addressed this challenge by combining samples collected within the BIO-NMD consortium from four geographically dispersed clinical sites to identify protein markers associated with muscular dystrophy using an antibody bead array platform with 384 antibodies. Based on concordance in statistical significance and confirmatory results obtained from analysis of both serum and plasma, we identified eleven proteins associated with muscular dystrophy, among which four proteins were elevated in blood from muscular dystrophy patients: carbonic anhydrase III (CA3) and myosin light chain 3 (MYL3), both specifically expressed in slow-twitch muscle fibers and mitochondrial malate dehydrogenase 2 (MDH2) and electron transfer flavo-protein A (ETFA). Using age-matched sub-cohorts, 9 protein profiles correlating with disease progression and severity were identified, which hold promise for the development of new clinical tools for management of dystrophinopathies.

  • 19.
    Ayoglu, Burcu
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Gundberg, Anna
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Khademi, Mohsen
    Karolinska Hosp, Dept Clin Neurosci, Stockholm, Sweden..
    Olsson, Tomas
    Karolinska Hosp, Dept Clin Neurosci, Stockholm, Sweden..
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Proteomic profiling of the autoimmunity repertoire in multiple sclerosis2012Ingår i: New Biotechnology, ISSN 1871-6784, E-ISSN 1876-4347, Vol. 29, s. S20-S20Artikel i tidskrift (Övrigt vetenskapligt)
  • 20.
    Ayoglu, Burcu
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Häggmark, Anna
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Khademi, M.
    Olsson, T.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Autoantibody profiling in multiple sclerosis using arrays of human protein fragments2013Ingår i: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 12, nr 9, s. 2657-2672Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Profiling the autoantibody repertoire with large antigen collections is emerging as a powerful tool for the identification of biomarkers for autoimmune diseases. Here, a systematic and undirected approach was taken to screen for profiles of IgG in human plasma from 90 individuals with multiple sclerosis related diagnoses. Reactivity pattern of 11,520 protein fragments (representing ̃38% of all human protein encoding genes) were generated on planar protein microarrays built within the Human Protein Atlas. For more than 2,000 antigens IgG reactivity was observed, among which 64% were found only in single individuals. We used reactivity distributions among multiple sclerosis subgroups to select 384 antigens, which were then reevaluated on planar microarrays, corroborated with suspension bead arrays in a larger cohort (n = 376) and confirmed for specificity in inhibition assays. Among the heterogeneous pattern within and across multiple sclerosis subtypes, differences in recognition frequencies were found for 51 antigens, which were enriched for proteins of transcriptional regulation. In conclusion, using protein fragments and complementary high-throughput protein array platforms facilitated an alternative route to discovery and verification of potentially disease-associated autoimmunity signatures, that are now proposed as additional antigens for large-scale validation studies across multiple sclerosis biobanks.

  • 21.
    Ayoglu, Burcu
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Häggmark, Anna
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Neiman, Maja
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Igel, Ulrika
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Schwenk, Jochen
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Systematic antibody and antigen-based proteomic profiling with microarrays2011Ingår i: EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, ISSN 1473-7159, Vol. 11, nr 2, s. 219-234Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Current approaches within affinity-based proteomics are driven both by the accessibility and availability of antigens and capture reagents, and by suitable multiplexed technologies onto which these are implemented. By combining planar microarrays and other multiparallel systems with sets of reagents, possibilities to discover new and unpredicted protein disease associations, either via directed hypothesis-driven or via undirected hypothesis-generating target selection, can be created. In the following stages, the discoveries made during these screening phases have to be verified for potential clinical relevance based on both technical and biological aspects. The use of affinity tools throughout discovery and verification has the potential to streamline the introduction of new markers, as transition into clinically required assay formats appears straightforward. In this article, we summarize some of the current building blocks within array-and affinity-based proteomic profiling with a focus on body fluids, by giving a perspective on how current and upcoming developments in this bioscience could enable a path of pursuit for biomarker discovery.

  • 22.
    Ayoglu, Burcu
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Kockum, Ingrid
    Olsson, Tomas
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Anoctamin 2 identified as an autoimmune target in multiple sclerosis2016Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, s. 10-10Artikel i tidskrift (Övrigt vetenskapligt)
  • 23.
    Ayoglu, Burcu
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mitsios, N.
    Khademi, M.
    Alfredsson, L.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mulder, J.
    Olsson, T.
    Schwenk, Jochen
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Anoctamin 2, a novel autoimmune target candidate in multiple sclerosis2014Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, s. 49-50Artikel i tidskrift (Övrigt vetenskapligt)
  • 24.
    Ayoglu, Burcu
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mitsios, N.
    Karolinska Inst, Neurosci, Stockholm, Sweden..
    Kockum, I.
    Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Olsson, T.
    Karolinska Inst, Clin Neurosci, Stockholm, Sweden..
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Anoctamin 2 identified as an autoimmune target in multiple sclerosis2016Ingår i: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 23, s. 57-57Artikel i tidskrift (Övrigt vetenskapligt)
  • 25.
    Ayoglu, Burcu
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Multiplexed antigen bead arrays for the assessment of antibody selectivity and epitope mapping2018Ingår i: Epitope Mapping Protocols, Humana Press Inc. , 2018, s. 239-248Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    With the increasing number of binding reagents for affinity-based investigations of the human proteome, high-throughput tools for the characterization of the used reagents become essential. For the analysis of binding selectivity, bead-based antigen arrays offer a miniaturized and parallelized assay platform to meet such needs, as they enable two-dimensional multiplexing to analyze up to 384 samples against up to 500 analytes in a single round of analysis. In this chapter, we describe our protocols for the generation of multiplex bead arrays built on immobilized protein fragments, as well as biotinylated peptides. Combined together, these two versions of antigen arrays offer a versatile approach for multiplexed characterization of antibody binding selectivity, off-target interactions, as well as mapping for the amino acids of epitopes involved in antibody binding.

  • 26.
    Ayoglu, Burcu
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Antigen arrays for profiling autoantibody repertoires2016Ingår i: Bioanalysis, ISSN 1757-6180, E-ISSN 1757-6199, Vol. 8, nr 10, s. 1105-1126Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Autoantibodies are a key component for the diagnosis, prognosis and monitoring of various diseases. In order to discover novel autoantibody targets, highly multiplexed assays based on antigen arrays hold a great potential and provide possibilities to analyze hundreds of body fluid samples for their reactivity pattern against thousands of antigens in parallel. Here, we provide an overview of the available technologies for producing antigen arrays, highlight some of the technical and methodological considerations and discuss their applications as discovery tools. Together with recent studies utilizing antigen arrays, we give an overview on how the different types of antigen arrays have and will continue to deliver novel insights into autoimmune diseases among several others.

  • 27.
    Ayoglu, Burcu
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Sjöberg, Ronald
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    et al.,
    The calcium-activated chloride channel anoctamine 2 as an autoimmune component of multiple sclerosisManuskript (preprint) (Övrigt vetenskapligt)
  • 28.
    Bachmann, Julie
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Burte, Florence
    Pramana, Setia
    Conte, Ianina
    Brown, Biobele J.
    Orimadegun, Adebola E.
    Ajetunmobi, Wasiu A.
    Afolabi, Nathaniel K.
    Akinkunmi, Francis
    Omokhodion, Samuel
    Akinbami, Felix O.
    Shokunbi, Wuraola A.
    Kampf, Caroline
    Pawitan, Yudi
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Sodeinde, Olugbemiro
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Wahlgren, Mats
    Fernandez-Reyes, Delmiro
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Affinity Proteomics Reveals Elevated Muscle Proteins in Plasma of Children with Cerebral Malaria2014Ingår i: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 10, nr 4, s. e1004038-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria.

  • 29.
    Bedri, Sahl Khalid
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Nilsson, Ola B.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Advice Foretagsassistans & Stockholm AB, TCER AB, Stockholm, Sweden..
    Fink, Katharina
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Neurol, Stockholm, Sweden..
    Månberg, Anna
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Affin Prote, SciLifeLab, Stockholm, Sweden..
    Hamsten, Carl
    Karolinska Inst, Dept Med, Immunol & Allergy Unit, Stockholm, Sweden..
    Ayoglu, Burcu
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Affin Prote, SciLifeLab, Stockholm, Sweden..
    Manouchehrinia, Ali
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Affin Prote, SciLifeLab, Stockholm, Sweden..
    Olsson, Tomas
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Hillert, Jan
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Grönlund, Hans
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Glaser, Anna
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Plasma protein profiling reveals candidate biomarkers for multiple sclerosis treatment2019Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 14, nr 5, artikel-id e0217208Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Multiple sclerosis (MS) treatment options have improved significantly over the past decades, but the consequences of MS can still be devastating and the needs for monitoring treatment surveillance are considerable. In the current study we used affinity proteomics technology to identify potential biomarkers which could ultimately be used to as facilitate treatment decisions. We profiled the intra-individual changes in the levels of 59 target proteins using an antibody suspension bead array in serial plasma samples from 44 MS patients during treatment with natalizumab followed by fingolimod. Nine proteins showed decreasing plasma levels during natalizumab treatment, with PEBP1 and RTN3 displaying the most significant changes. Protein levels remained stable during fingolimod treatment for both proteins. The decreasing PEBP1 levels during natalizumab treatment could be validated using ELISA and replicated in an independent cohort. These results support the use of this technology as a high throughput method of identifying potentially useful biomarkers of MS treatment.

  • 30.
    Berglund, Lisa
    et al.
    KTH, Skolan för bioteknologi (BIO).
    Björling, Erik
    KTH, Skolan för bioteknologi (BIO).
    Gry, Marcus
    KTH, Skolan för bioteknologi (BIO).
    Asplund, Anna
    Uppsala Univ, Rudbeck laboratory.
    Al-Khalili Szigyarto, Cristina
    KTH, Skolan för bioteknologi (BIO).
    Persson, Anja
    KTH, Skolan för bioteknologi (BIO).
    Ottoson, Jenny
    KTH, Skolan för bioteknologi (BIO).
    Wernérus, Henrik
    KTH, Skolan för bioteknologi (BIO).
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO).
    Sivertsson, Åsa
    KTH, Skolan för bioteknologi (BIO).
    Wester, Kenneth
    Uppsala Univ, Rudbeck laboratory.
    Kampf, Caroline
    Uppsala Univ, Rudbeck laboratory.
    Hober, Sophia
    KTH, Skolan för bioteknologi (BIO).
    Pontén, Fredrik
    Uppsala Univ, Rudbeck laboratory.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO).
    Generation of validated antibodies towards the human proteomeArtikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Here we show the results from a large effort to generate antibodies towards the human proteome. A high-throughput strategy was developed based on cloning and expression of antigens as recombitant protein epitope signature tags (PrESTs) Affinity purified polyclonal antibodies were generated, followed by validation by protein microarrays, Western blotting and microarray-based immunohistochemistry. PrESTs were selected based on sequence uniqueness relative the proteome and a bioinformatics analysis showed that unique antigens can be found for at least 85% of the proteome using this general strategy. The success rate from antigen selection to validated antibodies was 31%, and from protein to antibody 55%. Interestingly, membrane-bound and soluble proteins performed equally and PrEST lengths between 75 and 125 amino acids were found to give the highest yield of validated antibodies. Multiple antigens were selected for many genes and the results suggest that specific antibodies can be systematically generated to most human proteibs.

  • 31.
    Berglund, Lisa
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Björling, Erik
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Oksvold, Per
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Fagerberg, Linn
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Al-Khalili Szigyarto, Cristina
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Persson, Anja
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Ottosson, Jenny
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Wernérus, Henrik
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Lundberg, Emma
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Sivertsson, Åsa
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Hober, Sophia
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    et al.,
    A genecentric human protein atlas for expression profiles based on antibodies2008Ingår i: Molecular & Cellular Proteomics, ISSN 1535-9476, Vol. 7, nr 10, s. 2019-2027Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    An attractive path forward in proteomics is to experimentally annotate the human protein complement of the genome in a genecentric manner. Using antibodies, it might be possible to design protein-specific probes for a representative protein from every protein-coding gene and to subsequently use the antibodies for systematical analysis of cellular distribution and subcellular localization of proteins in normal and disease tissues. A new version (4.0) of the Human Protein Atlas has been developed in a genecentric manner with the inclusion of all human genes and splice variants predicted from genome efforts together with a visualization of each protein with characteristics such as predicted membrane regions, signal peptide, and protein domains and new plots showing the uniqueness (sequence similarity) of every fraction of each protein toward all other human proteins. The new version is based on tissue profiles generated from 6120 antibodies with more than five million immunohistochemistry-based images covering 5067 human genes, corresponding to similar to 25% of the human genome. Version 4.0 includes a putative list of members in various protein classes, both functional classes, such as kinases, transcription factors, G-protein-coupled receptors, etc., and project-related classes, such as candidate genes for cancer or cardiovascular diseases. The exact antigen sequence for the internally generated antibodies has also been released together with a visualization of the application-specific validation performed for each antibody, including a protein array assay, Western blot analysis, immunohistochemistry, and, for a large fraction, immunofluorescence-based confocal microscopy. New search functionalities have been added to allow complex queries regarding protein expression profiles, protein classes, and chromosome location. The new version of the protein atlas thus is a resource for many areas of biomedical research, including protein science and biomarker discovery.

  • 32.
    Bergman, Peter
    et al.
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Lab Med, Clin Microbiol, Stockholm, Sweden..
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hober, Sophia
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Aleman, Soo
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Med Huddinge, Infect Dis, Stockholm, Sweden..
    Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial2021Ingår i: EBioMedicine, E-ISSN 2352-3964, Vol. 74, s. 103705-, artikel-id 103705Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls. Methods: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection. Findings: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively. Interpretation: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity.

  • 33.
    Bergström, Jonas P.
    et al.
    AstraZeneca R&D, Sweden.
    Gry, Marcus
    AstraZeneca R&D, Sweden.
    Lengqvist, Johan
    AstraZeneca R&D, Sweden.
    Lindberg, Johan
    AstraZeneca R&D, Sweden.
    Schwenk, Jochen
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Drobin, Kimi
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Watkins, Paul B.
    The Hamner Institutes for Health Science, United States.
    Schuppe Koistinen, Ina
    AstraZeneca R&D, Sweden.
    Novel DILI biomarkers for prediction of acetaminophen-induced human hepatotoxicity2012Ingår i: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, s. S76-S76Artikel i tidskrift (Övrigt vetenskapligt)
  • 34.
    Bergström, Sofia
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Linn, Öijerstedt
    Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, Solna, Sweden; Unit for Hereditary Dementias, Theme Aging, Karolinska University Hospital, Solna, Sweden.
    Remnestål, Julia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Olofsson, Jennie
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Ullgren, Abbe
    Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, Solna, Sweden..
    Seelaar, Harro
    Department of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands.
    van Swieten, John C
    Department of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands.
    Synofzik, Matthis
    Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany; Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
    Sanchez-Valle, Raquel
    Alzheimer’s disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d’Investigacións Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain.
    Moreno, Fermin
    Cognitive Disorders Unit, Department of Neurology, Donostia University Hospital, San Sebastian, Gipuzkoa, Spain; Neuroscience Area, Biodonostia Health Research Institute, San Sebastian, Gipuzkoa, Spain.
    Finger, Elizabeth
    Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada.
    Masellis, Mario
    Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, Canada.
    Tartaglia, Carmela
    Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada.
    Vandenberghe, Rik
    Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium; Neurology Service, University Hospitals Leuven, Belgium; Leuven Brain Institute, KU Leuven, Leuven, Belgium.
    Laforce, Robert
    Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques, CHU de Québec, and Faculté de Médecine, Université Laval, QC, Canada.
    Galimberti, Daniela
    Fondazione IRCCS Ospedale Policlinico, Milan, Italy; University of Milan, Centro Dino Ferrari, Milan, Italy.
    Borroni, Barbara
    Centre for Neurodegenerative Disorders, Department of Clinical and Experimental Sciences, University of Brescia, Italy.
    Butler, Chris R
    Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, UK; Department of Brain Sciences, Imperial College London, UK.
    Gerhard, Alexander
    Division of Neuroscience and Experimental Psychology, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK; Departments of Geriatric Medicine and Nuclear Medicine, University of Duisburg- Essen, Germany.
    Ducharme, Simon
    Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Québec, Canada; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Québec, Canada.
    Rohrer, Jonathan D
    Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, Queen Square, London, UK.
    Månberg, Anna
    Division of Affinity Proteomics, Department of Protein Science, KTH Royal Institute of Technology, SciLifeLab, Stockholm, Sweden.
    Graff, Caroline
    Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, Solna, Sweden; Unit for Hereditary Dementias, Theme Aging, Karolinska University Hospital, Solna, Sweden.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI studyManuskript (preprint) (Övrigt vetenskapligt)
  • 35.
    Bergström, Sofia
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Oijerstedt, Linn
    Swedish FTD Initiat, Stockholm, Sweden.;Karolinska Univ Hosp, Theme Aging, Unit Hereditary Dementias, Dept Neurobiol Care Sci & Soc,Div Neurogeriatr,Ka, Solna, Sweden.;Karolinska Univ Hosp, Unit Hereditary Dementias, Theme Aging, Solna, Sweden..
    Remnestål, Julia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Olofsson, Jennie
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Ullgren, Abbe
    Swedish FTD Initiat, Stockholm, Sweden.;Karolinska Univ Hosp, Theme Aging, Unit Hereditary Dementias, Dept Neurobiol Care Sci & Soc,Div Neurogeriatr,Ka, Solna, Sweden..
    Seelaar, Harro
    Erasmus MC, Dept Neurol, Rotterdam, Netherlands..
    van Swieten, John C.
    Erasmus MC, Dept Neurol, Rotterdam, Netherlands..
    Synofzik, Matthis
    Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany.;Univ Tubingen, Ctr Neurol, Tubingen, Germany.;Ctr Neurodegenerat Dis DZNE, Tubingen, Germany..
    Sanchez-Valle, Raquel
    Univ Barcelona, Inst Invest Biomed August Pi I Sunyer, Hosp Clin, Alzheimers Dis & Other Cognit Disorders Unit,Neur, Barcelona, Spain..
    Moreno, Fermin
    Donostia Univ Hosp, Dept Neurol, Cognit Disorders Unit, San Sebastian, Gipuzkoa, Spain.;Biodonostia Hlth Res Inst, Neurosci Area, San Sebastian, Gipuzkoa, Spain..
    Finger, Elizabeth
    Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada..
    Masellis, Mario
    Univ Toronto, Sunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Toronto, ON, Canada..
    Tartaglia, Carmela
    Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada..
    Vandenberghe, Rik
    Katholieke Univ Leuven, Lab Cognit Neurol, Dept Neurosci, Leuven, Belgium.;Univ Hosp Leuven, Neurol Serv, Leuven, Belgium.;Katholieke Univ Leuven, Leuven Brain Inst, Leuven, Belgium..
    Laforce, Robert
    Univ Laval, CHU Quebec, Dept Sci Neurol, Clin Interdisciplinaire Mem, Quebec City, PQ, Canada.;Univ Laval, Fac Med, Quebec City, PQ, Canada..
    Galimberti, Daniela
    Fdn IRCCS Osped Policlin, Milan, Italy.;Univ Milan, Ctr Dino Ferrari, Milan, Italy..
    Borroni, Barbara
    Univ Brescia, Ctr Neurodegenerat Disorders, Dept Clin & Expt Sci, Brescia, Italy..
    Butler, Chris R.
    Univ Oxford, Nuffield Dept Clin Neurosci, Med Sci Div, Oxford, England.;Imperial Coll London, Dept Brain Sci, London, England..
    Gerhard, Alexander
    Univ Manchester, Wolfson Mol Imaging Ctr, Div Neurosci & Expt Psychol, Manchester, Lancs, England.;Univ Duisburg Essen, Dept Geriatr Med, Duisburg, Germany.;Univ Duisburg Essen, Dept Nucl Med, Duisburg, Germany..
    Ducharme, Simon
    McGill Univ, Douglas Mental Hlth Univ Inst, Dept Psychiat, Montreal, PQ, Canada.;McGill Univ, McConnell Brain Imaging Ctr, Montreal Neurol Inst, Montreal, PQ, Canada..
    Rohrer, Jonathan D.
    UCL Inst Neurol, Dementia Res Ctr, Dept Neurodegenerat Dis, Queen Sq, London, England..
    Manberg, Anna
    Univ Toronto, Sunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Toronto, ON, Canada..
    Graff, Caroline
    Swedish FTD Initiat, Stockholm, Sweden.;Karolinska Univ Hosp, Theme Aging, Unit Hereditary Dementias, Dept Neurobiol Care Sci & Soc,Div Neurogeriatr,Ka, Solna, Sweden.;Karolinska Univ Hosp, Unit Hereditary Dementias, Theme Aging, Solna, Sweden..
    Nilsson, Peter
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI study2021Ingår i: Molecular Neurodegeneration, E-ISSN 1750-1326, Vol. 16, nr 1, artikel-id 79Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background A detailed understanding of the pathological processes involved in genetic frontotemporal dementia is critical in order to provide the patients with an optimal future treatment. Protein levels in CSF have the potential to reflect different pathophysiological processes in the brain. We aimed to identify and evaluate panels of CSF proteins with potential to separate symptomatic individuals from individuals without clinical symptoms (unaffected), as well as presymptomatic individuals from mutation non-carriers. Methods A multiplexed antibody-based suspension bead array was used to analyse levels of 111 proteins in CSF samples from 221 individuals from families with genetic frontotemporal dementia. The data was explored using LASSO and Random forest. Results When comparing affected individuals with unaffected individuals, 14 proteins were identified as potentially important for the separation. Among these, four were identified as most important, namely neurofilament medium polypeptide (NEFM), neuronal pentraxin 2 (NPTX2), neurosecretory protein VGF (VGF) and aquaporin 4 (AQP4). The combined profile of these four proteins successfully separated the two groups, with higher levels of NEFM and AQP4 and lower levels of NPTX2 in affected compared to unaffected individuals. VGF contributed to the models, but the levels were not significantly lower in affected individuals. Next, when comparing presymptomatic GRN and C9orf72 mutation carriers in proximity to symptom onset with mutation non-carriers, six proteins were identified with a potential to contribute to a separation, including progranulin (GRN). Conclusion In conclusion, we have identified several proteins with the combined potential to separate affected individuals from unaffected individuals, as well as proteins with potential to contribute to the separation between presymptomatic individuals and mutation non-carriers. Further studies are needed to continue the investigation of these proteins and their potential association to the pathophysiological mechanisms in genetic FTD.

  • 36.
    Bergström, Sofia
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Remnestål, Julia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Olofsson, Jennie
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Markaki, Ioanna
    Karolinska Institutet.
    Carvalho, Stephanie
    Institut du Cerveau et de la Moelle épinière, Sorbonne Université.
    Corvol, Jean-Christophe
    Institut du Cerveau et de la Moelle épinière, Sorbonne Université.
    Kultima, Kim
    Uppsala Universitet.
    Kilander, Lena
    Uppsala Universitet.
    Löwenmark, Malin
    Uppsala Universitet.
    Ingelsson, Martin
    Uppsala Universitet.
    Blennow, Kaj
    Sahlgrenska University Hospital, University of Gothenburg.
    Zetterberg, Henrik
    Sahlgrenska University Hospital, University of Gothenburg; Department of Neurodegenerative Disease, UCL Institute of Neurology, London; UK Dementia Research Institute at UCL, London.
    Nellgård, Bengt
    Sahlgrenska University Hospital, University of Gothenburg.
    Brosseron, Frederic
    Universitätsklinikum, Bonn; German Center for Neurodegenerative Diseases (DZNE), Bonn.
    Heneka, Michael
    Universitätsklinikum, Bonn.
    Bosch, Beatriz
    University of Barcelona.
    Sanches-Valle, Raquel
    University of Barcelona.
    Månberg, Anna
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Svenningsson, Per
    Karolinska Institutet.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Multi-cohort protein profiling reveals higher levels of six brain-enriched proteins in Alzheimer’s disease patientsManuskript (preprint) (Övrigt vetenskapligt)
  • 37.
    Bergström, Sofia
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Remnestål, Julia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Yousef, Jamil
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Olofsson, Jennie
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Markaki, Ioanna
    Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden.
    Carvalho, Stephanie
    Sorbonne Université Institut du Cerveau ‐ Paris Brain Institute ‐ ICM, Assistance‐Publique Hôpitaux de Paris INSERM CNRS Hôpital Pitié‐Salpêtrière Department of Neurology Centre d’Investigation Clinique Neurosciences Paris France.
    Corvol, Jean‐Christophe
    Sorbonne Université Institut du Cerveau ‐ Paris Brain Institute ‐ ICM, Assistance‐Publique Hôpitaux de Paris INSERM CNRS Hôpital Pitié‐Salpêtrière Department of Neurology Centre d’Investigation Clinique Neurosciences Paris France.
    Kultima, Kim
    Department of Medical Sciences Clinical Chemistry Uppsala University Uppsala Sweden.
    Kilander, Lena
    Department of Public Health and Caring Sciences Geriatrics Uppsala University Uppsala Sweden.
    Löwenmark, Malin
    Department of Public Health and Caring Sciences Geriatrics Uppsala University Uppsala Sweden.
    Ingelsson, Martin
    Department of Public Health and Caring Sciences Geriatrics Uppsala University Uppsala Sweden.
    Blennow, Kaj
    Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy University of Gothenburg;Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden.
    Zetterberg, Henrik
    Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy University of Gothenburg;Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden;Department of Neurodegenerative Disease UCL Institute of Neurology London UK;UK Dementia Research Institute at UCL London UK.
    Nellgård, Bengt
    Anesthesiology and Intensive Care Medicine Sahlgrenska University Hospital Mölndal Sweden;Department of Anesthesiology and Intensive Care Medicine Institute of Clinical Sciences The Sahlgrenska Academy University of Gothenburg.
    Brosseron, Frederic
    Universitätsklinikum Bonn Germany;German Center for Neurodegenerative Diseases (DZNE) Bonn Germany.
    Heneka, Michael T.
    Universitätsklinikum Bonn Germany.
    Bosch, Beatriz
    Alzheimer’s and other cognitive disorders Unit. Service of Neurology Hospital Clínic de Barcelona Institut d'Investigació Biomèdica August Pi i Sunyer University of Barcelona Barcelona Spain.
    Sanchez‐Valle, Raquel
    Alzheimer’s and other cognitive disorders Unit. Service of Neurology Hospital Clínic de Barcelona Institut d'Investigació Biomèdica August Pi i Sunyer University of Barcelona Barcelona Spain.
    Månberg, Anna
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Svenningsson, Per
    Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Multi‐cohort profiling reveals elevated CSF levels of brain‐enriched proteins in Alzheimer’s disease2021Ingår i: Annals of Clinical and Translational Neurology, E-ISSN 2328-9503, Vol. 8, nr 7, s. 1456-1470Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Decreased amyloid beta (Ab) 42 together with increased tau and phospho-tau in cerebrospinal fluid (CSF) is indicative of Alzheimer’s disease (AD). However, the molecular pathophysiology underlying the slowly progressive cognitive decline observed in AD is not fully understood and it is not known what other CSF biomarkers may be altered in early disease stages. Methods: We utilized an antibody-based suspension bead array to analyze levels of 216 proteins in CSF from AD patients, patients with mild cognitive impairment (MCI), and controls from two independent cohorts collected within the AETIONOMY consortium. Two additional cohorts from Sweden were used for biological verification. Results: Six proteins, amphiphysin (AMPH), aquaporin 4 (AQP4), cAMP-regulated phosphoprotein 21 (ARPP21), growth-associated protein 43 (GAP43), neurofilament medium polypeptide (NEFM), and synuclein beta (SNCB) were found at increased levels in CSF from AD patients compared with controls. Next, we used CSF levels of Ab42 and tau for the stratification of the MCI patients and observed increased levels of AMPH, AQP4, ARPP21, GAP43, and SNCB in the MCI subgroups with abnormal tau levels compared with controls. Further characterization revealed strong to moderate correlations between these five proteins and tau concentrations. Interpretation: In conclusion, we report six extensively replicated candidate biomarkers with the potential to reflect disease development. Continued evaluation of these proteins will determine to what extent they can aid in the discrimination of MCI patients with and without an underlying AD etiology, and if they have the potential to contribute to a better understanding of the AD continuum.

  • 38. Birse, Kenzie D.
    et al.
    Romas, Laura M.
    Guthrie, Brandon L.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Bosire, Rose
    Kiarie, James
    Farquhar, Carey
    Broliden, Kristina
    Burgener, Adam D.
    Genital Injury Signatures and Microbiome Alterations Associated With Depot Medroxyprogesterone Acetate Usage and Intravaginal Drying Practices2017Ingår i: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 215, nr 4, s. 590-598Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Increasing evidence suggests depot medroxyprogesterone acetate (DMPA) and intravaginal practices may be associated with human immunodeficiency virus (HIV-1) infection risk; however, the mechanisms are not fully understood. This study evaluated the effect of DMPA and intravaginal practices on the genital proteome and microbiome to gain mechanistic insights. Methods. Cervicovaginal secretions from 86 Kenyan women, including self-reported DMPA users (n = 23), nonhormonal contraceptive users (n = 63), and women who practice vaginal drying (n = 46), were analyzed using tandem-mass spectrometry. Results. We identified 473 human and 486 bacterial proteins from 18 different genera. Depot medroxyprogesterone acetate use associated with increased hemoglobin and immune activation (HBD, HBB, IL36G), and decreased epithelial repair proteins (TFF3, F11R). Vaginal drying associated with increased hemoglobin and decreased phagocytosis factors (AZU1, MYH9, PLAUR). Injury signatures were exacerbated in DMPA users who also practiced vaginal drying. More diverse (H index: 0.71 vs 0.45; P =.009) bacterial communities containing Gardnerella vaginalis associated with vaginal drying, whereas DMPA showed no significant association with community composition or diversity. Conclusions. These findings provide new insights into the impact of DMPA and vaginal drying on mucosal barriers. Future investigations are needed to confirm their relationship with HIV risk in women.

  • 39. Blixt, L.
    et al.
    Bogdanovic, G.
    Buggert, M.
    Gao, Y.
    Hober, Sophia
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Healy, K.
    Johansson, H.
    Kjellander, C.
    Mravinacová, Sára
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Muschiol, S.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Palma, M.
    Pin, Elisa
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Smith, C. I. E.
    Stromberg, O.
    Sällberg Chen, M.
    Zain, R.
    Hansson, L.
    Österborg, A.
    Covid-19 in patients with chronic lymphocytic leukemia: clinical outcome and B- and T-cell immunity during 13 months in consecutive patients2022Ingår i: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 36, nr 2, s. 476-481Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We studied clinical and immunological outcome of Covid-19 in consecutive CLL patients from a well-defined area during month 1–13 of the pandemic. Sixty patients (median age 71 y, range 43–97) were identified. Median CIRS was eight (4–20). Patients had indolent CLL (n = 38), had completed (n = 12) or ongoing therapy (n = 10). Forty-six patients (77%) were hospitalized due to severe Covid-19 and 11 were admitted to ICU. Severe Covid-19 was equally distributed across subgroups irrespective of age, gender, BMI, CLL status except CIRS (p < 0.05). Fourteen patients (23%) died; age ≥75 y was the only significant risk factor (p < 0.05, multivariate analysis with limited power). Comparing month 1–6 vs 7–13 of the pandemic, deaths were numerically reduced from 32% to 18%, ICU admission from 37% to 15% whereas hospitalizations remained frequent (86% vs 71%). Seroconversion occurred in 33/40 patients (82%) and anti-SARS-CoV-2 antibodies were detectable at six and 12 months in 17/22 and 8/11 patients, respectively. Most (13/17) had neutralizing antibodies and 19/28 had antibodies in saliva. SARS-CoV-2-specific T-cells (ELISpot) were detected in 14/17 patients. Covid-19 continued to result in high admission even among consecutive and young early- stage CLL patients. A robust and durable B and/or T cell immunity was observed in most convalescents.

  • 40.
    Blixt, Lisa
    et al.
    Karolinska Univ Hosp Solna, Dept Hematol, Stockholm, Sweden.;Karolinska Inst, Ctr Infect Med, Dept Oncol Pathol, Stockholm, Sweden..
    Gao, Yu
    Karolinska Inst, Ctr Infect Med, Dept Med Huddinge, Stockholm, Sweden..
    Wullimann, David
    Karolinska Inst, Ctr Infect Med, Dept Med Huddinge, Stockholm, Sweden..
    Ingelman-Sundberg, Hanna Muren
    Karolinska Inst, Ctr Infect Med, Dept Oncol Pathol, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Oncol, Stockholm, Sweden..
    Muschiol, Sandra
    Karolinska Univ Hosp Solna, Dept Clin Microbiol, Stockholm, Sweden.;Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden..
    Healy, Katie
    Karolinska Inst, Dept Dent Med, Huddinge, Sweden..
    Bogdanovic, Gordana
    Karolinska Univ Hosp Solna, Dept Clin Microbiol, Stockholm, Sweden.;Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden..
    Pin, Elisa
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Kjellander, Christian
    Karolinska Inst, Dept Lab Med, Stockholm, Sweden.;Capio St Goran Hosp, Dept Internal Med, Stockholm, Sweden..
    Grifoni, Alba
    La Jolla Inst Immunol, Ctr Infect Dis & Vaccine Res, La Jolla, CA USA..
    Sette, Alessandro
    La Jolla Inst Immunol, Ctr Infect Dis & Vaccine Res, La Jolla, CA USA.;Univ Calif San Diego, Div Infect Dis & Global Publ Hlth, Dept Med, San Diego, CA USA..
    Chen, Margaret Sallberg
    Karolinska Inst, Dept Dent Med, Huddinge, Sweden..
    Ljunggren, Hans -Gustaf
    Karolinska Inst, Ctr Infect Med, Dept Med Huddinge, Stockholm, Sweden..
    Buggert, Marcus
    Karolinska Inst, Ctr Infect Med, Dept Med Huddinge, Stockholm, Sweden..
    Hansson, Lotta
    Karolinska Inst, Ctr Infect Med, Dept Oncol Pathol, Stockholm, Sweden..
    Osterborg, Anders
    Karolinska Univ Hosp Solna, Dept Hematol, Stockholm, Sweden.;Karolinska Inst, Ctr Infect Med, Dept Oncol Pathol, Stockholm, Sweden..
    Hybrid immunity in immunocompromised patients with CLL after SARS-CoV-2 infection followed by booster mRNA vaccination2022Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 140, nr 22, s. 2403-2407Artikel i tidskrift (Refereegranskat)
  • 41.
    Blom, Kim
    et al.
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, S-18288 Stockholm, Sweden.;Publ Hlth Agcy Sweden, Stockholm, Sweden..
    Marking, Ulrika
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, S-18288 Stockholm, Sweden..
    Havervall, Sebastian
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, S-18288 Stockholm, Sweden..
    Norin, Nina Greilert
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, S-18288 Stockholm, Sweden..
    Gordon, Max
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, S-18288 Stockholm, Sweden..
    Garcia, Marina
    Publ Hlth Agcy Sweden, Stockholm, Sweden.;Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden..
    Tecleab, Teghesti
    Publ Hlth Agcy Sweden, Stockholm, Sweden..
    Christ, Wanda
    Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden..
    Forsell, Mattias
    Umeå Univ, Dept Clin Microbiol, Umeå, Sweden..
    Phillipson, Mia
    Uppsala Univ, Dept Med Cell Biol, Uppsala, Sweden.;Uppsala Univ, Sci Life Lab, Uppsala, Sweden..
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Mangsbo, Sara
    Uppsala Univ, Sci Life Lab, Uppsala, Sweden.;Uppsala Univ, Dept Pharm, Uppsala, Sweden..
    Hober, Sophia
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Aberg, Mikael
    Uppsala Univ, Sci Life Lab, Uppsala, Sweden.;Uppsala Univ, Dept Med Sci Clin Chem, Uppsala, Sweden..
    Klingstrom, Jonas
    Publ Hlth Agcy Sweden, Stockholm, Sweden.;Karolinska Inst, Dept Med Huddinge, Ctr Infect Med, Stockholm, Sweden..
    Thalin, Charlotte
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, S-18288 Stockholm, Sweden..
    Immune responses after omicron infection in triple-vaccinated health-care workers with and without previous SARS-CoV-2 infection2022Ingår i: The Lancet - Infectious diseases, ISSN 1473-3099, E-ISSN 1474-4457, Vol. 22, nr 7, s. 943-945Artikel i tidskrift (Refereegranskat)
  • 42.
    Bradley, Frideborg
    et al.
    Karolinska Univ Hosp, Ctr Mol Med, Karolinska Inst, Dept Med Solna,Div Infect Dis,Dept Infect Dis, Stockholm, Sweden..
    Boger, Mathias Franzen
    Karolinska Univ Hosp, Ctr Mol Med, Karolinska Inst, Dept Med Solna,Div Infect Dis,Dept Infect Dis, Stockholm, Sweden..
    Kaldhusdal, Vilde
    Karolinska Univ Hosp, Ctr Mol Med, Karolinska Inst, Dept Med Solna,Div Infect Dis,Dept Infect Dis, Stockholm, Sweden..
    Ahlberg, Alexandra
    Karolinska Univ Hosp, Ctr Mol Med, Karolinska Inst, Dept Med Solna,Div Infect Dis,Dept Infect Dis, Stockholm, Sweden..
    Edfeldt, Gabriella
    Karolinska Univ Hosp, Ctr Mol Med, Karolinska Inst, Dept Med Solna,Div Infect Dis,Dept Infect Dis, Stockholm, Sweden..
    Lajoie, Julie
    Univ Manitoba, Dept Med Microbiol & Infect Dis, Winnipeg, MB, Canada.;Univ Nairobi, Dept Med Microbiol, Nairobi, Kenya..
    Bergström, Sofia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Omollo, Kenneth
    Univ Nairobi, Dept Med Microbiol, Nairobi, Kenya..
    Damdimopoulos, Anastasios
    Karolinska Inst, Dept Biosci & Nutr, Bioinformat & Express Anal Core Facil, Huddinge, Sweden..
    Czarnewski, Paulo
    Stockholm Univ, Dept Biochem & Biophys, SciLifeLab, Natl Bioinformat Infrastruct Sweden, Solna, Sweden..
    Månberg, Anna
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Oyugi, Julius
    Univ Manitoba, Dept Med Microbiol & Infect Dis, Winnipeg, MB, Canada.;Univ Nairobi, Dept Med Microbiol, Nairobi, Kenya..
    Kimani, Joshua
    Univ Manitoba, Dept Med Microbiol & Infect Dis, Winnipeg, MB, Canada.;Univ Nairobi, Dept Med Microbiol, Nairobi, Kenya.;Partners Hlth & Dev Africa, Nairobi, Kenya..
    Nilsson, Peter
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Fowke, Keith
    Univ Manitoba, Dept Med Microbiol & Infect Dis, Winnipeg, MB, Canada.;Univ Nairobi, Dept Med Microbiol, Nairobi, Kenya.;Partners Hlth & Dev Africa, Nairobi, Kenya.;Univ Manitoba, Dept Community Hlth Sci, Winnipeg, MB, Canada..
    Tjernlund, Annelie
    Karolinska Univ Hosp, Ctr Mol Med, Karolinska Inst, Dept Med Solna,Div Infect Dis,Dept Infect Dis, Stockholm, Sweden..
    Broliden, Kristina
    Karolinska Univ Hosp, Ctr Mol Med, Karolinska Inst, Dept Med Solna,Div Infect Dis,Dept Infect Dis, Stockholm, Sweden..
    Multi-omics analysis of the cervical epithelial integrity of women using depot medroxyprogesterone acetate2022Ingår i: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 18, nr 5, artikel-id e1010494Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Depot medroxyprogesterone acetate (DMPA) is an injectable hormonal contraceptive used by millions of women worldwide. However, experimental studies have associated DMPA use with genital epithelial barrier disruption and mucosal influx of human immunodeficiency virus (HIV) target cells. We explored the underlying molecular mechanisms of these findings. Ectocervical biopsies and cervicovaginal lavage (CVL) specimens were collected from HIV-seronegative Kenyan sex workers using DMPA (n = 32) or regularly cycling controls (n = 64). Tissue samples were assessed by RNA-sequencing and quantitative imaging analysis, whereas protein levels were measured in CVL samples. The results suggested a DMPA-associated upregulation of genes involved in immune regulation, including genes associated with cytokine-mediated signaling and neutrophil-mediated immunity. A transcription factor analysis further revealed DMPA-associated upregulation of RELA and NFKB1 which are involved in several immune activation pathways. Several genes significantly downregulated in the DMPA versus the control group were involved in epithelial structure and function, including genes encoding keratins, small proline-rich proteins, and cell-cell adhesion proteins. Pathway analyses indicated DMPA use was associated with immune activation and suppression of epithelium development, including keratinization and cornification processes. The cervicovaginal microbiome composition (Lactobacillus dominant and non-Lactobacillus dominant) had no overall interactional impact on the DMPA associated tissue gene expression. Imaging analysis verified that DMPA use was associated with an impaired epithelial layer as illustrated by staining for the selected epithelial junction proteins E-cadherin, desmoglein-1 and claudin-1. Additional staining for CD4(+) cells revealed a more superficial location of these cells in the ectocervical epithelium of DMPA users versus controls. Altered protein levels of SERPINB1 and ITIH2 were further observed in the DMPA group. Identification of specific impaired epithelial barrier structures at the gene expression level, which were verified at the functional level by tissue imaging analysis, illustrates mechanisms by which DMPA adversely may affect the integrity of the genital mucosa. Author summarySexual transmission accounts for the majority of all new HIV infections in women, and alterations to the mucosal environment of the female genital tract have been associated with an increase in the risk of acquiring HIV. Observational epidemiological studies have implied that the use of the injectable hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may be associated with increased HIV-acquisition. However, a prospective clinical study has not confirmed this association and the controversial findings are currently evaluated in the context of international reproductive health policies. Several studies using various model systems indicate that DMPA affects the integrity of the genital epithelial barrier as well as the mucosal immune system, but the exact mechanisms remain largely unknown. To characterize the effect of DMPA on the genital mucosal environment, we used a multi-omics approach to assess paired genital secretions and cervical tissue samples from long-term regular DMPA users living in Kenya. This unique cohort represents a population at risk of HIV infection in which DMPA is one of the most commonly used hormonal contraceptives. We identified impaired cervical epithelial barrier structures, including DMPA-associated reduction in the expression of cell-cell adhesion molecules, keratins, small proline-rich proteins and a thinner upper epithelial layer with more superficially located CD4(+) cells. Gene set enrichment pathway analyses indicated DMPA use was associated with immune activation and suppression of epithelium development including keratinization and cornification pathways. Protein analysis identified altered levels of selected anti-proteases. Our findings illustrate mechanisms by which DMPA adversely may affect the integrity of the genital mucosa.

  • 43.
    Bremer, Hanna D.
    et al.
    Swedish Univ Agr Sci, Dept Clin Sci, SE-75007 Uppsala, Sweden..
    Landegren, Nils
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, CMM, L8 01, SE-17176 Stockholm, Sweden.;Uppsala Univ, Dept Med Sci, Sci Life Lab, Uppsala, Sweden..
    Sjöberg, Ronald
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hallgren, Asa
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, CMM, L8 01, SE-17176 Stockholm, Sweden..
    Renneker, Stefanie
    Euroimmun AG, D-23560 Lubeck, Germany..
    Lattwein, Erik
    Euroimmun AG, D-23560 Lubeck, Germany..
    Leonard, Dag
    Uppsala Univ, Rheumatol & Sci Life Lab, Dept Med Sci, SE-75185 Uppsala, Sweden..
    Eloranta, Maija-Leena
    Uppsala Univ, Rheumatol & Sci Life Lab, Dept Med Sci, SE-75185 Uppsala, Sweden..
    Ronnblom, Lars
    Uppsala Univ, Rheumatol & Sci Life Lab, Dept Med Sci, SE-75185 Uppsala, Sweden..
    Nordmark, Gunnel
    Uppsala Univ, Rheumatol & Sci Life Lab, Dept Med Sci, SE-75185 Uppsala, Sweden..
    Nilsson, Peter
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Andersson, Goran
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75007 Uppsala, Sweden..
    Lilliehook, Inger
    Swedish Univ Agr Sci, Dept Clin Sci, SE-75007 Uppsala, Sweden..
    Lindblad-Toh, Kerstin
    Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.;Uppsala Univ, Sci Life Lab, IMBIM, SE-75123 Uppsala, Sweden..
    Kampe, Olle
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, CMM, L8 01, SE-17176 Stockholm, Sweden.;Uppsala Univ, Dept Med Sci, Sci Life Lab, Uppsala, Sweden.;Univ Bergen, Dept Clin Sci, N-5021 Bergen, Norway.;Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, N-5021 Bergen, Norway.;Haukeland Hosp, Dept Med, N-5021 Bergen, Norway..
    Hansson-Hamlin, Helene
    Swedish Univ Agr Sci, Dept Clin Sci, SE-75007 Uppsala, Sweden..
    ILF2 and ILF3 are autoantigens in canine systemic autoimmune disease2018Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 8, artikel-id 4852Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dogs can spontaneously develop complex systemic autoimmune disorders, with similarities to human autoimmune disease. Autoantibodies directed at self-antigens are a key feature of these autoimmune diseases. Here we report the identification of interleukin enhancer-binding factors 2 and 3 (ILF2 and ILF3) as autoantigens in canine immune-mediated rheumatic disease. The ILF2 autoantibodies were discovered in a small, selected canine cohort through the use of human protein arrays; a method not previously described in dogs. Subsequently, ILF3 autoantibodies were also identified in the same cohort. The results were validated with an independent method in a larger cohort of dogs. ILF2 and ILF3 autoantibodies were found exclusively, and at a high frequency, in dogs that showed a speckled pattern of antinuclear antibodies on immunofluorescence. ILF2 and ILF3 autoantibodies were also found at low frequency in human patients with SLE and Sjogren's syndrome. These autoantibodies have the potential to be used as diagnostic biomarkers for canine, and possibly also human, autoimmune disease.

  • 44.
    Bronge, M.
    et al.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Asplund Hogelin, K.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Thomas, O. G.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Ruhrmann, S.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Carvalho-Querioz, C.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Nilsson, O.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Kaiser, A.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Holmgren, E.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Linnerbauer, M.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Adzemovic, M. Z.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Zeitelhofer, M.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Hellström, Cecilia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Jelcic, I.
    Univ Hosp Zurich, Neuroimmunol & MS Res, Zurich, Switzerland..
    Liu, Hailong
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Fiber- och polymerteknologi, Polymerteknologi.
    Nilsson, Peter
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Hillert, J.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Brundin, L.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Fink, K.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Martin, R.
    Univ Hosp Zurich, Neuroimmunol & MS Res, Zurich, Switzerland..
    Tegel, Hanna
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinteknologi.
    Gräslund, Torbjörn
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinvetenskap.
    Al Nimer, F.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Guerreiro-Cacais, A. O.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Khademi, M.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Gafvelin, G.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Olsson, T.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Gronlund, H.
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    T cell reactivity screening reveals four novel CNS autoantigens in multiple sclerosis2021Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 27, nr 2_SUPPL, s. 344-345Artikel i tidskrift (Övrigt vetenskapligt)
  • 45.
    Bronge, Mattias
    et al.
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Therapeut Immune Design, S-17176 Stockholm, Sweden..
    Hogelin, Klara Asplund
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Neuroimmunol Unit, S-17176 Stockholm, Sweden..
    Thomas, Olivia G.
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Therapeut Immune Design, S-17176 Stockholm, Sweden..
    Ruhrmann, Sabrina
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Therapeut Immune Design, S-17176 Stockholm, Sweden..
    Carvalho-Queiroz, Claudia
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Therapeut Immune Design, S-17176 Stockholm, Sweden..
    Nilsson, Ola B.
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Therapeut Immune Design, S-17176 Stockholm, Sweden..
    Kaiser, Andreas
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Therapeut Immune Design, S-17176 Stockholm, Sweden..
    Zeitelhofer, Manuel
    Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, S-17177 Stockholm, Sweden..
    Holmgren, Erik
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Therapeut Immune Design, S-17176 Stockholm, Sweden..
    Linnerbauer, Mathias
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Neuroimmunol Unit, S-17176 Stockholm, Sweden..
    Adzemovic, Milena Z.
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Neuroimmunol Unit, S-17176 Stockholm, Sweden..
    Hellström, Cecilia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Jelcic, Ivan
    Univ Zurich, Univ Hosp Zurich, Neuroimmunol & MS Res Sect NIMS, Neurol Clin, CH-8091 Zurich, Switzerland..
    Liu, Hao
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Nilsson, Peter
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Hillert, Jan
    Karolinska Inst, Karolinska Univ Hosp, Dept Clin Neurosci, Div Neurol, S-17176 Stockholm, Sweden..
    Brundin, Lou
    Karolinska Inst, Karolinska Univ Hosp, Dept Clin Neurosci, Div Neurol, S-17176 Stockholm, Sweden..
    Fink, Katharina
    Karolinska Inst, Karolinska Univ Hosp, Dept Clin Neurosci, Div Neurol, S-17176 Stockholm, Sweden..
    Kockum, Ingrid
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Neuroimmunol Unit, S-17176 Stockholm, Sweden..
    Tengvall, Katarina
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Neuroimmunol Unit, S-17176 Stockholm, Sweden.;Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, S-75237 Uppsala, Sweden..
    Martin, Roland
    Univ Zurich, Univ Hosp Zurich, Neuroimmunol & MS Res Sect NIMS, Neurol Clin, CH-8091 Zurich, Switzerland..
    Tegel, Hanna
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Gräslund, Torbjörn
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinvetenskap.
    Al Nimer, Faiez
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Neuroimmunol Unit, S-17176 Stockholm, Sweden..
    Guerreiro-Cacais, Andre Ortlieb
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Neuroimmunol Unit, S-17176 Stockholm, Sweden..
    Khademi, Mohsen
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Neuroimmunol Unit, S-17176 Stockholm, Sweden..
    Gafvelin, Guro
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Therapeut Immune Design, S-17176 Stockholm, Sweden..
    Olsson, Tomas
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Neuroimmunol Unit, S-17176 Stockholm, Sweden..
    Gronlund, Hans
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Therapeut Immune Design, S-17176 Stockholm, Sweden..
    Identification of four novel T cell autoantigens and personal autoreactive profiles in multiple sclerosis2022Ingår i: Science Advances, E-ISSN 2375-2548, Vol. 8, nr 17, artikel-id eabn1823Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), in which pathological T cells, likely autoimmune, play a key role. Despite its central importance, the autoantigen repertoire remains largely uncharacterized. Using a novel in vitro antigen delivery method combined with the Human Protein Atlas library, we screened for T cell autoreactivity against 63 CNS-expressed proteins. We identified four previously unreported autoantigens in MS: fatty acid-binding protein 7, prokineticin-2, reticulon-3, and synaptosomal-associated protein 91, which were verified to induce interferon-gamma responses in MS in two cohorts. Autoreactive profiles were heterogeneous, and reactivity to several autoantigens was MS-selective. Autoreactive T cells were predominantly CD4(+) and human leukocyte antigen-DR restricted. Mouse immunization induced antigen-specific responses and CNS leukocyte infiltration. This represents one of the largest systematic efforts to date in the search for MS autoantigens, demonstrates the heterogeneity of autoreactive profiles, and highlights promising targets for future diagnostic tools and immunomodulatory therapies in MS.

  • 46. Brouns, Stan J. J.
    et al.
    Walther, Jasper
    Snijders, Ambrosius P. L.
    de Werken, Harmen J. G. van
    Willemen, Hanneke L. D. M.
    Worm, Petra
    de Vos, Marjon G. J.
    Andersson, Anders
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Lundgren, Magnus
    Mazon, Hortense F. M.
    van den Heuvel, Robert H. H.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Salmon, Laurent
    de Vos, Willem M.
    Wright, Phillip C.
    Bernander, Rolf
    van der Oost, John
    Identification of the missing links in prokaryotic pentose oxidation pathways - Evidence for enzyme recruitment2006Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 281, nr 37, s. 27378-27388Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The pentose metabolism of Archaea is largely unknown. Here, we have employed an integrated genomics approach including DNA microarray and proteomics analyses to elucidate the catabolic pathway for D-arabinose in Sulfolobus solfataricus. During growth on this sugar, a small set of genes appeared to be differentially expressed compared with growth on D-glucose. These genes were heterologously overexpressed in Escherichia coli, and the recombinant proteins were purified and biochemically studied. This showed that D-arabinose is oxidized to 2-oxoglutarate by the consecutive action of a number of previously uncharacterized enzymes, including a D-arabinose dehydrogenase, a D-arabinonate dehydratase, a novel 2-keto-3-deoxy-D-arabinonate dehydratase, and a 2,5-dioxopentanoate dehydrogenase. Promoter analysis of these genes revealed a palindromic sequence upstream of the TATA box, which is likely to be involved in their concerted transcriptional control. Integration of the obtained biochemical data with genomic context analysis strongly suggests the occurrence of pentose oxidation pathways in both Archaea and Bacteria, and predicts the involvement of additional enzyme components. Moreover, it revealed striking genetic similarities between the catabolic pathways for pentoses, hexaric acids, and hydroxyproline degradation, which support the theory of metabolic pathway genesis by enzyme recruitment.

  • 47. Buus, S.
    et al.
    Rockberg, Johan
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Forsström, Björn
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Schafer-Nielsen, C.
    High-resolution mapping of linear antibody epitopes using ultrahigh-density peptide microarrays2012Ingår i: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 11, nr 12, s. 1790-1800Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Antibodies empower numerous important scientific, clinical, diagnostic, and industrial applications. Ideally, the epitope(s) targeted by an antibody should be identified and characterized, thereby establishing antibody reactivity, highlighting possible cross-reactivities, and perhaps even warning against unwanted (e.g. autoimmune) reactivities. Antibodies target proteins as either conformational or linear epitopes. The latter are typically probed with peptides, but the cost of peptide screening programs tends to prohibit comprehensive specificity analysis. To perform high-throughput, high-resolution mapping of linear antibody epitopes, we have used ultrahigh-density peptide microarrays generating several hundred thousand different peptides per array. Using exhaustive length and substitution analysis, we have successfully examined the specificity of a panel of polyclonal antibodies raised against linear epitopes of the human proteome and obtained very detailed descriptions of the involved specificities. The epitopes identified ranged from 4 to 12 amino acids in size. In general, the antibodies were of exquisite specificity, frequently disallowing even single conservative substitutions. In several cases, multiple distinct epitopes could be identified for the same target protein, suggesting an efficient approach to the generation of paired antibodies. Two alternative epitope mapping approaches identified similar, although not necessarily identical, epitopes. These results show that ultrahigh-density peptide microarrays can be used for linear epitope mapping. With an upper theoretical limit of 2,000,000 individual peptides per array, these peptide microarrays may even be used for a systematic validation of antibodies at the proteomic level.

  • 48.
    Byström, Sanna
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Ayoglu, Burcu
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Häggmark, Anna
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hong, Mun-Gwan
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Drobin, Kim
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Forsström, Björn
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Fredolini, Claudia
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    et al.,
    Affinity Proteomic Profiling of Plasma, Cerebrospinal Fluid, and Brain Tissue within Multiple Sclerosis2014Ingår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 13, nr 11, s. 4607-4619Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The brain is a vital organ and because it is well shielded from the outside environment, possibilities for noninvasive analysis are often limited. Instead, fluids taken from the spinal cord or circulatory system are preferred sources for the discovery of candidate markers within neurological diseases. In the context of multiple sclerosis (MS), we applied an affinity proteomic strategy and screened 22 plasma samples with 4595 antibodies (3450 genes) on bead arrays, then defined 375 antibodies (334 genes) for targeted analysis in a set of 172 samples and finally used 101 antibodies (43 genes) on 443 plasma as well as 573 cerebrospinal spinal fluid (CSF) samples. This revealed alteration of protein profiles in relation to MS subtypes for IRF8, IL7, METTL14, SLC30A7, and GAP43. Respective antibodies were subsequently used for immunofluorescence on human post-mortem brain tissue with MS pathology for expression and association analysis. There, antibodies for IRF8, IL7, and METTL14 stained neurons in proximity of lesions, which highlighted these candidate protein targets for further studies within MS and brain tissue. The affinity proteomic translation of profiles discovered by profiling human body fluids and tissue provides a powerful strategy to suggest additional candidates to studies of neurological disorders.

  • 49.
    Carapito, Raphael
    et al.
    Univ Strasbourg, Transplantex NG,Plateforme GENOMAX, Inst Themat Interdisciplinaire ITI Med Precis Str, Fac Med,UMR S 1109,INSERM,Lab ImmunoRhumatol Mol, F-67085 Strasbourg, France.;Nouvel Hop Civil, Serv Immunol Biol, Pole Biol, Plateau Tech Biol, F-67091 Strasbourg, France.;Federat Hosp Univ FHU OMICARE, Ctr Rech Immunol & Hematol, Federat Med Translat Strasbourg FMTS, F-67085 Strasbourg, France..
    Pin, Elisa
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Chittenden, Thomas W.
    Genuity Sci, Genuity AI Res Inst, Boston, MA 02114 USA.;Harvard Med Sch, Boston Childrens Hosp, Div Genet & Genom, Boston, MA 02115 USA..
    Bahram, Seiamak
    Univ Strasbourg, Transplantex NG,Plateforme GENOMAX, Inst Themat Interdisciplinaire ITI Med Precis Str, Fac Med,UMR S 1109,INSERM,Lab ImmunoRhumatol Mol, F-67085 Strasbourg, France.;Nouvel Hop Civil, Serv Immunol Biol, Pole Biol, Plateau Tech Biol, F-67091 Strasbourg, France.;Federat Hosp Univ FHU OMICARE, Ctr Rech Immunol & Hematol, Federat Med Translat Strasbourg FMTS, F-67085 Strasbourg, France..
    Identification of driver genes for critical forms of COVID-19 in a deeply phenotyped young patient cohort2022Ingår i: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 14, nr 628, artikel-id eabj7521Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The drivers of critical coronavirus disease 2019 (COVID-19) remain unknown. Given major confounding factors such as age and comorbidities, true mediators of this condition have remained elusive. We used a multi-omics analysis combined with artificial intelligence in a young patient cohort where major comorbidities were excluded at the onset. The cohort included 47 "critical" (in the intensive care unit under mechanical ventilation) and 25 "non-critical" (in a non-critical care ward) patients with COVID-19 and 22 healthy individuals. The analyses included whole-genome sequencing, whole-blood RNA sequencing, plasma and blood mononuclear cell proteomics, cytokine profiling, and high-throughput immunophenotyping. An ensemble of machine learning, deep learning, quantum annealing, and structural causal modeling were used. Patients with critical COVID-19 were characterized by exacerbated inflammation, perturbed lymphoid and myeloid compartments, increased coagulation, and viral cell biology. Among differentially expressed genes, we observed up-regulation of the metalloprotease ADAM9. This gene signature was validated in a second independent cohort of 81 critical and 73 recovered patients with COVID-19 and was further confirmed at the transcriptional and protein level and by proteolytic activity. Ex vivo ADAM9 inhibition decreased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uptake and replication in human lung epithelial cells. In conclusion, within a young, otherwise healthy, cohort of individuals with COVID-19, we provide the landscape of biological perturbations in vivo where a unique gene signature differentiated critical from non-critical patients. We further identified ADAM9 as a driver of disease severity and a candidate therapeutic target.

  • 50. Catharina, Johansson
    et al.
    Maria, Mikus
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO).
    Nathalie, Acevedo
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO).
    Annika, Scheynius
    Profiling the autoantibody repertoire in atopic dermatitis identifies four associated autoantigens2017Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 86, nr 4, s. 322-322Artikel i tidskrift (Övrigt vetenskapligt)
1234567 1 - 50 av 316
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