title: Inborn errors of human IL-17 immunity underlie chronic mucocutaneous candidiasis.
abstract: OBJECTIVE
  Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent symptomatic infection of the nails, skin and mucosae mostly by Candida albicans. CMC is common in patients with profound primary T-cell immunodeficiency, who often display multiple infectious and autoimmune diseases. Patients with syndromic CMC, including autosomal dominant hyper IgE syndrome (AD-HIES) and autosomal recessive autoimmune polyendocrinopathy syndrome type I (APS-I), display fewer other infections. Patients with isolated CMC (CMCD) rarely display any other severe disease. We review here recent progress in the genetic dissection of these three types of inherited CMC.
  
  
  RESULTS
  Low IL-17 T-cell proportions were reported in patients with AD-HIES bearing heterozygous STAT3 mutations, prone to CMC and staphylococcal diseases, and in a kindred with autosomal recessive CARD9 deficiency, prone to CMC and other fungal infections. High levels of neutralizing autoantibodies against IL-17 cytokines were documented in patients with APS-I presenting with CMC as their only infectious disease. The first three genetic causes of CMCD were then reported: autosomal recessive IL-17RA and autosomal dominant IL-17F deficiencies and autosomal dominant STAT1 gain-of-function, impairing IL-17-producing T-cell development.
  
  
  CONCLUSIONS
  Inborn errors of human IL-17 immunity underlie CMC. Impaired IL-17 immunity may therefore account for CMC in other settings, including patients with acquired immunodeficiency.
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm U980 and University Paris Descartes, Necker Medical School, Paris Sorbonne Cité, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
authors.forename: Sophie
authors.initials: S
authors.lastname: Cypowyj
authors.forename: László
authors.initials: L
authors.lastname: Maródi
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D002176:Candida albicans / Q000276:immunology; D002178:Candidiasis, Chronic Mucocutaneous / Q000235:genetics / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D007589:Job Syndrome / Q000235:genetics / Q000276:immunology*; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics / Q000276:immunology*; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000276:immunology*; D050791:STAT Transcription Factors / Q000235:genetics / Q000276:immunology
chemical_list: C109985:IL17RA protein, human; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D050791:STAT Transcription Factors