| Anti-cytokine autoantibodies suggest pathogenetic links with autoimmune regulator deficiency in humans and mice. | |
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MedLine Citation:
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PMID: 23379432 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 they neutralize 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 with chronic mucocutaneous candidiasis in both syndromes. Here, we demonstrate that the immunoglobulin (Ig)Gs but not the IgAs in APECED sera are responsible for neutralizing IFN-ω, IFN-α2a, 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-α2a appeared mainly conformational. We also found mainly IgG1 neutralizing autoantibodies 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 deficiency is not simply a mere side effect of chronic mucosal Candida infection, but appears to be related more closely to disease initiation. |
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Authors:
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J Kärner; A Meager; M Laan; J Maslovskaja; M Pihlap; A Remm; E Juronen; A S B Wolff; E S Husebye; K T Podkrajšek; N Bratanic; T Battelino; N Willcox; P Peterson; K Kisand |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Clinical and experimental immunology Volume: 171 ISSN: 1365-2249 ISO Abbreviation: Clin. Exp. Immunol. Publication Date: 2013 Mar |
Date Detail:
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Created Date: 2013-02-05 Completed Date: 2013-04-02 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0057202 Medline TA: Clin Exp Immunol Country: England |
Other Details:
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Languages: eng Pagination: 263-72 Citation Subset: IM |
Copyright Information:
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© 2012 British Society for Immunology. |
Affiliation:
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Molecular Pathology Group, University of Tartu, Tartu, Estonia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autoantibodies / blood, immunology* Cytokines / immunology* Humans Immunodominant Epitopes Immunoglobulin G / blood Interferon-alpha / immunology Interleukin-17 / immunology Interleukins / immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Polyendocrinopathies, Autoimmune / immunology* Transcription Factors / deficiency*, physiology |
| Chemical | |
Reg. No./Substance:
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0/APECED protein; 0/Autoantibodies; 0/Cytokines; 0/IL17A protein, human; 0/Immunodominant Epitopes; 0/Immunoglobulin G; 0/Interferon-alpha; 0/Interleukin-17; 0/Interleukins; 0/Transcription Factors; 0/interleukin-22 |
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