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.
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.
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.
aLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm U980 and University Paris Descartes, Necker Medical School, Paris Sorbonne Cité, Paris, France, EU
bLaboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, USA
cDepartment of Infectious and Paediatric Immunology, University of Debrecen Medical and Health Science Centre, Debrecen, Hungary, EU
dStudy Centre for Primary Immunodeficiencies, Assistance Publique Hôpitaux de Paris, Necker Hospital, Paris, France, EU
Correspondence to Anne Puel, Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm U980 and University Paris Descartes, Necker Medical School, Paris Sorbonne Cité, 156 rue de Vaugirard, 75015 Paris, France, EU. Tel: +33 1 40 61 53 87; e-mail: firstname.lastname@example.org