HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines.

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.
AuthorsKai Kisand, Anette S Bøe Wolff, Katarina Trebusak Podkrajsek, Liina Tserel, Maire Link, Kalle V Kisand, Elisabeth Ersvaer, Jaakko Perheentupa, Martina Moter Erichsen, Nina Bratanic, Antonella Meloni, Filomena Cetani, Roberto Perniola, Berrin Ergun-Longmire, Noel Maclaren, Kai J E Krohn, Mikulás Pura, Berthold Schalke, Philipp Ströbel, Maria Isabel Leite, Tadej Battelino, Eystein S Husebye, Pärt Peterson, Nick Willcox, Anthony Meager
JournalThe Journal of experimental medicine (J Exp Med) Vol. 207 Issue 2 Pg. 299-308 (Feb 15 2010) ISSN: 1540-9538 [Electronic] United States
PMID20123959 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Neutralizing
  • Autoantibodies
  • Interleukin-17
  • Interleukins
  • interleukin-22
Topics
  • Antibodies, Neutralizing (immunology)
  • Arthritis, Rheumatoid (blood, immunology)
  • Autoantibodies (immunology)
  • Autoimmunity
  • Candidiasis, Chronic Mucocutaneous (immunology)
  • Cell Differentiation
  • Humans
  • Interleukin-17 (antagonists & inhibitors, immunology, metabolism)
  • Interleukins (antagonists & inhibitors, immunology, metabolism)
  • Lupus Erythematosus, Systemic (blood, immunology)
  • Mutation
  • Polyendocrinopathies, Autoimmune (immunology)
  • Psoriasis (blood, immunology)
  • Self Tolerance
  • T-Lymphocyte Subsets (immunology)
  • Thymoma (immunology)
  • Thymus Neoplasms (immunology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: