Kisand, Kai and Wolff, Anette S. Boe and Podkrajsek, Katarina Trebusak and Tserel, Liina and Link, Maire and Kisand, Kalle V. and Ersvaer, Elisabeth and Perheentupa, Jaakko and Erichsen, Martina Moter and Bratanic, Nina and Meloni, Antonella and Cetani, Filomena and Perniola, Roberto and Ergun-Longmire, Berrin and Maclaren, Noel and Krohn, Kai J. E. and Pura, Mikulas and Schalke, Berthold and Stroebel, Philipp and Leite, Maria Isabel and Battelino, Tadej and Husebye, Eystein S. and Peterson, Paert and Willcox, Nick and Meager, Anthony (2010) Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines. JOURNAL OF EXPERIMENTAL MEDICINE, 207 (2). pp. 299-308. ISSN 0022-1007,
Full text not available from this repository. (Request a copy)Abstract
Chronic mucocutaneous candidiasis (CMC) is frequently associated with T cell immunodeficiencies. Specifically, the proinflammatory IL-17A-producing Th17 subset is implicated in protection against fungi at epithelial surfaces. In autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED, or autoimmune polyendocrine syndrome 1), CMC is often the first sign, but the underlying immunodeficiency is a long-standing puzzle. In contrast, the subsequent endocrine features are clearly autoimmune, resulting from defects in thymic self-tolerance induction caused by mutations in the autoimmune regulator (AIRE). We report severely reduced IL-17F and IL-22 responses to both Candida albicans antigens and polyclonal stimulation in APECED patients with CMC. Surprisingly, these reductions are strongly associated with neutralizing autoantibodies to IL-17F and IL-22, whereas responses were normal and autoantibodies infrequent in APECED patients without CMC. Our multicenter survey revealed neutralizing autoantibodies against IL-17A (41%), IL-17F (75%), and/or IL-22 (91%) in > 150 APECED patients, especially those with CMC. We independently found autoantibodies against these Th17-produced cytokines in rare thymoma patients with CMC. The autoantibodies preceded the CMC in all informative cases. We conclude that IL-22 and IL-17F are key natural defenders against CMC and that the immunodeficiency underlying CMC in both patient groups has an autoimmune basis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MUCOSAL HOST-DEFENSE; HYPER-IGE SYNDROME; SYNDROME TYPE-I; T-HELPER-CELLS; TH17 CELLS; ECTODERMAL DYSTROPHY; FUNGAL-INFECTIONS; INTERLEUKIN 22; AIRE; EXPRESSION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Aug 2020 07:09 |
| Last Modified: | 06 Aug 2020 07:09 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25151 |
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