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  • 1. Abrahamsson, T. R.
    et al.
    Jakobsson, H. E.
    Andersson, Anders F.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Björkstén, B.
    Engstrand, Lars
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Jenmalm, M. C.
    Low gut microbiota diversity in early infancy precedes asthma at school age2014In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, no 6, p. 842-850Article in journal (Refereed)
    Abstract [en]

    Background Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age. Objective To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema. Methods The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1week, 1month and 12months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7years of age (ClinicalTrials.gov ID NCT01285830). Results Children developing asthma (n=8) had a lower diversity of the total microbiota than non-asthmatic children at 1week (P=0.04) and 1month (P=0.003) of age, whereas allergic rhinoconjunctivitis (n=13), eczema (n=12) and positive skin prick reactivity (n=14) at 7years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease. Conclusion and Clinical Relevance Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.

  • 2. Brandstrom, J.
    et al.
    Vetander, M.
    Lilja, G.
    Johansson, S. G. O.
    Sundqvist, A. -C
    Kalm, Frida
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. Karolinska Univ Hosp, Sweden.
    Nilsson, C.
    Nopp, A.
    Individually dosed omalizumab: an effective treatment for severe peanut allergy2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 4, p. 540-550Article in journal (Refereed)
    Abstract [en]

    Background Treatment with omalizumab has shown a positive effect on food allergies, but no dosages are established. Basophil allergen threshold sensitivity (CD-sens) can be used to objectively measure omalizumab treatment efficacy and correlates with the outcome of double-blind placebo-controlled food challenge to peanut. Objective To evaluate whether individualized omalizumab treatment monitored by CD-sens could be an effective intervention for suppression of allergic reactions to peanut. Methods Severely peanut allergic adolescents (n = 23) were treated with omalizumab for 8 weeks, and CD-sens was analysed before and after. Based on whether CD-sens was suppressed after 8 weeks, the patients either were subject to a peanut challenge or received eight more weeks with increased dose of omalizumab, followed by peanut challenge or another 8-week cycle of omalizumab. IgE and IgE-antibodies to peanut and its components were analysed before treatment. Results After individualized omalizumab treatment (8-24 weeks), all patients continued with an open peanut challenge with no (n = 18) or mild (n = 5) objective allergic symptoms. Patients (n = 15) needing an elevated omalizumab dose (ED) to suppress CD-sens had significantly higher CD-sens values at baseline 1.49 (0.44-20.5) compared to those (n = 8) who managed with normal dose (ND) 0.32 (0.24-5.5) (P < 0.01). Median ratios for Ara h 2 IgE-ab/IgE were significantly higher in the ED group (17%) compared to the ND group (11%). Conclusions and Clinical Relevance Individually dosed omalizumab, monitored by CD-sens, is an effective and safe treatment for severe peanut allergy. The ratio of IgE-ab to storage protein Ara h 2/IgE as well as CD-sens to peanut may predict the need of a higher omalizumab dose.

  • 3.
    Thunberg, Sarah
    et al.
    Karolinska Institutet.
    Akdis, M.
    SIAF, Switzerland.
    Akdis, C. A.
    SIAF, Switzerland.
    Gronneberg, R.
    Karolinska institutet, Sweden.
    Malmstrom, V.
    Karolinska institutet, Sweden.
    Trollmo, C.
    Karolinska institutet, Sweden.
    van Hage, M.
    Karolinska institutet, Sweden.
    Gafvelin, G.
    Karolinska institutet, Sweden.
    Immune regulation by CD4(+)CD25(+) T cells and interleukin-10 in birch pollen-allergic patients and non-allergic controls2007In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 37, no 8, p. 1127-1136Article in journal (Refereed)
    Abstract [en]

    CD4(+)CD25(+) regulatory T (Treg) cells and the cytokines IL-10 or TGF-beta play key roles in the maintenance of T cell homeostasis and tolerance to infectious and non-infectious antigens such as allergens. To investigate the regulation of immune responses to birch pollen allergen compared with influenza antigen by Treg cells obtained from birch pollen-allergic patients and non-allergic controls. Peripheral blood was collected from 10 birch pollen-allergic patients and 10 non-allergic healthy controls. CD4(+)CD25(+) and CD4(+)CD25(-) cells isolated by magnetic-activated cell sorting were co-cultured and stimulated with birch pollen extract or influenza vaccine in the absence or presence of anti-IL-10 or soluble TGF-beta RII. CD4(+)CD25(+) cells from non-allergic controls were able to suppress influenza antigen and birch pollen stimulated effector cell proliferation, whereas CD4(+)CD25(+) cells from allergic patients suppressed influenza antigen-, but not birch pollen-stimulated proliferation. The production of Th1 cytokines, but not Th2 cytokines, was suppressed by CD4(+)CD25(+) cells from both allergic patients and controls, upon stimulation with birch pollen extract. Neutralization of IL-10 led to significantly increased production of IFN-gamma in cultures with CD4(+)CD25(-) T effector cells. In addition, six-fold higher concentrations of TNF-alpha were detected after neutralization of IL-10 in both CD4(+)CD25(-) and CD4(+)CD25(+) cell cultures from allergic patients and controls. We demonstrate that the allergen-specific suppressive function of CD4(+)CD25(+) cells from allergic patients is impaired compared with non-allergic controls. Moreover, neutralization of IL-10 enhances the production of TNF-alpha, suggesting counter-acting properties of IL-10 and TNF-alpha, where IL-10 promotes tolerance and suppression by Treg cells and TNF-alpha promotes inflammatory responses.

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