title: Mucocutaneous candidiasis and autoimmunity against cytokines in APECED and thymoma patients: clinical and pathogenetic implications.
abstract: Much has been learnt about the mechanisms of thymic self-tolerance induction from work on both the rare autosomal recessive disease autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) and the autoimmune regulator (AIRE) protein mutated in this disease. Normally, AIRE drives low-level expression of huge numbers of peripheral tissue-specific antigens (TSAgs) in medullary thymic epithelial cells (mTECs), leading to the deletion of TSAg-reactive thymocytes maturing nearby. The very recently discovered neutralizing autoantibodies (autoAbs) against Th17-related cells and cytokines in two autoimmunity-related syndromes associated with AIRE-mutant thymi or AIRE-deficient thymomas help to explain the chronic mucocutaneous candidiasis (CMC) seen in both syndromes. The surprising parallels between these syndromes also demand new hypotheses and research into the consequences of AIRE deficiency and the ensuing autoimmunizing pathways, and suggest more appropriate treatment regimens as discussed in this review.
authors.affiliation: Molecular Pathology Group, Institute of General and Molecular Pathology, University of Tartu, Tartu, Estonia. kai.kisand@ut.ee
authors.forename: Kai
authors.initials: K
authors.lastname: Kisand
authors.forename: Desa
authors.initials: D
authors.lastname: Lilic
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Pärt
authors.initials: P
authors.lastname: Peterson
authors.forename: Anthony
authors.initials: A
authors.lastname: Meager
authors.forename: Nick
authors.initials: N
authors.lastname: Willcox
mesh_terms: D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics; D002178:Candidiasis, Chronic Mucocutaneous / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D016884:Polyendocrinopathies, Autoimmune / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D015995:Prevalence; D012306:Risk; D058504:Th17 Cells / Q000276:immunology; D013945:Thymoma / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D013953:Thymus Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D000096927:AIRE Protein
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D014157:Transcription Factors; D000096927:AIRE Protein