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  • Anti-cytokine autoantibodies suggest pathogenetic links with autoimmune regulator deficiency in humans and mice
    Kärner, J. ...
    Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a recessive disorder resulting from mutations in the autoimmune regulator (AIRE). The patients' autoantibodies recognize not ... only multiple organ-specific targets, but also many type I interferons (IFNs) and most T helper type 17 (Th17) cell-associated cytokines, whose biological actions theyneutralize in vitro. These anti-cytokine autoantibodies are highly disease-specific: otherwise, they have been found only in patients with thymomas, tumours of thymic epithelial cells that fail to express AIRE. Moreover, autoantibodies against Th17 cell-associated cytokines correlate withchronic mucocutaneous candidiasis in both syndromes. Here, we demonstrate that the immunoglobulin (Ig)Gs but not the IgAs in APECED sera are responsiblefor neutralizing IFN-Ž, IFN-Ž2a, interleukin (IL)-17A and IL-22. Their dominant subclasses proved to be IgG1 and, surprisingly, IgG4 without IgE, possibly implicating regulatory T cell responses and/or epithelia in their initiation in these AIRE-deficiency states. The epitopes on IL-22 and IFN-Ž2a appeared mainly conformational. We also found mainly IgG1 neutralizingautoantibodies to IL-17A in aged AIRE-deficient BALB/c mice - the first report of any target shared by these human and murine AIRE-deficiency states. We conclude that autoimmunization against cytokines in AIRE deficiencyis not simply a mere side effect of chronic mucosal Candida infection, but appears to be related more closely to disease initiation.
    Vir: Clinical and experimental immunology. - ISSN 0009-9104 (Vol. 171, iss. 3, mar. 2013, str. 263-272)
    Vrsta gradiva - članek, sestavni del
    Leto - 2013
    Jezik - angleški
    COBISS.SI-ID - 757676
    DOI

vir: Clinical and experimental immunology. - ISSN 0009-9104 (Vol. 171, iss. 3, mar. 2013, str. 263-272)
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