CMC is associated with an impaired Th17 cell response; however, it remains unclear whether decreased serum IL-17 and IL-22 levels are related to a defect in cytokine production or to neutralizing autoantibodies resulting from mutations in the <i>AIRE</i> gene.
We highlight the historical and recent knowledge of CMC in children, emphasizing recent insights into basic science aspects of the dectin pathway, IL-17 signaling, consequences of AIRE gene defects, and clinical aspects of inheritance, and features that distinguish the different syndromes.
Inborn errors of the immune system (primary immune deficiencies) can present with isolated CMC known as CMC disease (CMCD), which is most often found in patients with autoimmune polyendocrinopathy syndrome type 1 (APS1)/APECED or in patients with an underlying gain-of-function STAT1 mutation (GOF-STAT1).
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by biallelic autoimmune regulator (<i>AIRE</i>) mutations that manifests with chronic mucocutaneous candidiasis (CMC) and autoimmunity.
Autoimmune regulator (Aire) mutations result in autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), which manifests as multi-organ autoimmunity and chronic mucocutaneous candidiasis (CMC).
CMC may be part of a complex clinical phenotype like in patients with deficiencies of STAT3, IL-12Rβ1/IL-12p40 and APS-1 or may be the only or dominant phenotypic manifestation of disease which is referred to as CMC disease.
These observations suggest that iNKT cell deficiency is part of the CMC disease phenotype irrespective of the presence of AIRE gene mutations but does not appear to confer susceptibility to chronic Candida infections.
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.
CMC includes patients with AIRE gene mutations who have autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), and patients without known mutations.