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  • 1. Brändström, J.
    et al.
    Vetander, M.
    Lilja, G.
    Sundqvist, A.
    Kalm, Frida
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Johansson, S.
    Nilsson, C.
    Nopp, A.
    Peanut oral immunotherapy during omalizumab protection; a clinical trial on severely peanut allergic adolescents2017In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 72, p. 65-66Article in journal (Other academic)
  • 2. Hamsten, C.
    et al.
    Häggmark, Anna
    KTH.
    Grundstrom, J.
    Mikus, Maria
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Lindskog, C.
    Konradsen, J. R.
    Eklund, A.
    Pershagen, G.
    Wickman, M.
    Grunewald, J.
    Melen, E.
    Hedlin, G.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    van Hage, M.
    Protein profiles of CCL5, HPGDS, and NPSR1 in plasma reveal association with childhood asthma2016In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 71, no 9, p. 1357-1361Article in journal (Refereed)
    Abstract [en]

    Asthma is a common chronic childhood disease with many different phenotypes that need to be identified. We analyzed a broad range of plasma proteins in children with well-characterized asthma phenotypes to identify potential markers of childhood asthma. Using an affinity proteomics approach, plasma levels of 362 proteins covered by antibodies from the Human Protein Atlas were investigated in a total of 154 children with persistent or intermittent asthma and controls. After screening, chemokine ligand 5 (CCL5) hematopoietic prostaglandin D synthase (HPGDS) and neuropeptide S receptor 1 (NPSR1) were selected for further investigation. Significantly lower levels of both CCL5 and HPGDS were found in children with persistent asthma, while NPSR1 was found at higher levels in children with mild intermittent asthma compared to healthy controls. In addition, the protein levels were investigated in another respiratory disease, sarcoidosis, showing significantly higher NPSR1 levels in sera from sarcoidosis patients compared to healthy controls. Immunohistochemical staining of healthy tissues revealed high cytoplasmic expression of HPGDS in mast cells, present in stroma of both airway epithelia, lung as well as in other organs. High expression of NPSR1 was observed in neuroendocrine tissues, while no expression was observed in airway epithelia or lung. In conclusion, we have utilized a broad-scaled affinity proteomics approach to identify three proteins with altered plasma levels in asthmatic children, representing one of the first evaluations of HPGDS and NPSR1 protein levels in plasma.

  • 3. Neimert-Andersson, T.
    et al.
    Thunberg, Sarah
    Karolinska Institutet, Sweden.
    Swedin, L.
    Karolinska Institutet, Sweden.
    Wiedermann, U.
    Medical University Vienna, Austria.
    Jacobsson-Ekman, G.
    Karolinska Institutet, Sweden.
    Dahlen, S. -E
    Karolinska Institutet, Sweden.
    Scheynius, A.
    Karolinska Institutet, Sweden.
    Gronlund, H.
    Karolinska Institutet, Sweden.
    van Hage, M.
    Karolinska Institutet, Sweden.
    Gafvelin, G.
    Karolinska Institutet, Sweden.
    Carbohydrate-based particles reduce allergic inflammation in a mouse model for cat allergy2008In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 63, no 5, p. 518-526Article in journal (Refereed)
    Abstract [en]

    Background: Allergen-specific immunotherapy (ASIT) is the only treatment of allergic disease that gives long-lasting relief of symptoms. However, concerns for safety and efficiency have highlighted the need for improvement of the therapy. We have previously suggested carbohydrate-based particles (CBPs) as a novel adjuvant and allergen carrier for ASIT. Our aim of this study was to evaluate the therapeutic potential of CBPs in ASIT, employing a mouse model for cat allergy. Methods: BALB/c mice were subcutaneously immunized with the recombinant (r) cat allergen Fel d 1 followed by intranasal challenge with cat dander extract (CDE). The sensitized mice were therapeutically treated with rFel d 1 covalently coupled to CBPs (CBP-rFel d 1). Airway hyper-reactivity (AHR), infiltration of leucocytes in bronchoalveolar lavage (BAL) fluid, allergen-specific serum immunoglobulin levels and in vitro splenocyte responses were evaluated. Results: Mice treated with CBP-rFel d 1 showed reduced features of allergic inflammation. They responded with (i) significantly decreased AHR and infiltration of eosinophils in BAL fluid after CDE challenge, (ii) the serum level of rFel d 1-specific IgE was reduced and the level of IgG(2)a was more pronounced after CBP-rFel d 1 treatment, and (iii) there was also a tendency of decreased allergen-specific cellular response. Conclusions: Carbohydrate-based particles are effective tools as adjuvant and allergen carriers for use in ASIT and constitutes a promising strategy to improve allergy treatment.

  • 4.
    Thunberg, Sarah
    et al.
    Karolinska Institutet, Sweden.
    Gafvelin, G.
    Karolinska Institutet, Sweden.
    Nord, M.
    Karolinska Institutet, Sweden.
    Gronneberg, R.
    Karolinska Institutet, Sweden.
    Grunewald, J.
    Karolinska Institutet, Sweden.
    Eklund, A.
    Karolinska Institutet, Sweden.
    van Hage, M.
    Karolinska Institutet, Sweden.
    Allergen provocation increases TH2-cytokines and FOXP3 expression in the asthmatic lung2010In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 65, no 3, p. 311-318Article in journal (Refereed)
    Abstract [en]

    P>Background: Allergic asthma is caused by allergen-specific IgE and T-helper cell (Th) type 2 responses towards airborne allergens. The objective of this study was to investigate local and systemic regulatory mechanisms in the early asthmatic response to bronchial allergen provocation. Methods: Birch pollen-allergic patients with mild asthma (n = 13) and healthy nonallergic controls (n = 14) were subjected to bronchoalveolar lavage (BAL) and blood sampling. On patients BAL was performed twice: without preceding provocation (’before samples’) and 24 h after bronchial provocation with birch pollen allergen. Lymphocytes in BAL and peripheral blood mononuclear cells (PBMCs) were phenotyped by multi-colour flow cytometry and cytokines measured by cytometric bead array. Proliferation and secreted cytokines were analysed in allergen-stimulated PBMCs, CD25+ depleted PBMCs and PBMCs with IL-10 neutralizing antibodies. Results: The numbers of CD69+ and FOXP3+ lymphocytes were higher in BAL after compared with before allergen provocation in asthmatic patients. Moreover, allergen provocation increased expression of FOXP3 in CD4+CD25bright cells. The cytokine profile in BAL fluid from asthmatics revealed higher levels of IL-5, compared with the controls, and an increase in IL-5, IL-6, IL-9 and IL-10 after allergen provocation. Pollen allergen stimulated PBMC cultures from asthmatic patients produced elevated levels of IL-5 and IL-13 compared with the controls, which were not affected by depletion of CD25+ cells or IL-10 neutralization. Conclusion: Despite an increase in CD4+CD25bright cells expressing high levels of FOXP3 in response to bronchial allergen provocation, asthmatic patients exhibit enhanced levels of Th2 cytokines in the lung, which may indicate an inability among infiltrating cells to suppress Th2 responses.

  • 5.
    Thunberg, Sarah
    et al.
    Karolinska Institutet, Sweden.
    Neimert-Andersson, T.
    Karolinska Institutet, Sweden.
    Cheng, Q.
    Karolinska Institutet, Sweden.
    Wermeling, F.
    Karolinska Institutet, Sweden.
    Bergstrom, U.
    Uppsala university, Sweden.
    Swedin, L.
    Karolinska Institutet, Sweden.
    Dahlen, S. -E
    Karolinska Institutet, Sweden.
    Arner, E.
    Karolinska Institutet, Sweden.
    Scheynius, A.
    Karolinska Institutet, Sweden.
    Karlsson, M. C. I.
    Karolinska Institutet, Sweden.
    Gafvelin, G.
    Karolinska Institutet, Sweden.
    van Hage, M.
    Karolinska Institutet, Sweden.
    Gronlund, H.
    Karolinska Institutet, Sweden.
    Prolonged antigen-exposure with carbohydrate particle based vaccination prevents allergic immune responses in sensitized mice2009In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 64, no 6, p. 919-926Article in journal (Refereed)
    Abstract [en]

    Defined particles carrying tightly bound allergens at high density have been suggested as alternatives in allergy vaccination. Carbohydrate based particles (CBP), sized 2 mu m, provide a platform for covalent coupling of allergens. To investigate the mechanisms of antigen presentation by CBP, as well as cellular and humoral responses after vaccination with the major cat allergen Fel d 1, covalently coupled to CBP. Mice (n = 10/group) were subcutaneously vaccinated with CBP-rFel d 1, CBP or phosphate buffer saline (PBS) before sensitization with rFel d 1 and challenged with cat dander extract. Fluorescent and (75)Se-radiolabeled tracking of allergens and particles were performed with flow cytometry and whole-body autoradiography. Humoral, cellular and regulatory immune responses were analyzed by ELISA and flow cytometry. Cytokines were measured in bronchoalveolar lavage fluid and splenocyte cultures. CBP-rFel d 1 prevented induction of airway inflammation and induced allergen-specific T-cell anergy. CBP-rFel d 1 also induced rapid IgM and IgG1-responses compared with soluble rFel d 1. Particles were phagocytosed by antigen-presenting cells and transported to draining lymph nodes and spleen. Moreover, antigen coupled to CBP remained longer at the injection site compared with alum. Covalent coupling of rFel d 1 to CBP induces rapid antibody production, prevents induction of allergic immune responses and systemic allergen spreading. Thus, CBP comprise several attractive adjuvant features for use in allergy vaccination. Prolonged allergen exposure through covalent coupling to particles suitable for phagocytosis, provides an adjuvant for safer and efficient allergy vaccination.

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