Chronic mucocutaneous candidiasis (CMC) occurs in patients with mutations in genes affecting IL-17-mediated immunity, such as <i>STAT3, AIRE, RORC, CARD9, IL12B</i>, and <i>IL12RB1</i>, or gain of function (GOF) mutations in <i>STAT1</i>.
We, therefore, suggest that due to an additional neutrophil dependent defect CARD9 deficiency predisposes not only to chronic mucocutaneous candidiasis, but also to invasive chronic Candida infections, especially of the central nervous system.
Inborn errors of interleukin-17 immunity have recently been shown to underlie chronic mucocutaneous candidiasis (CMC), while inborn errors of caspase recruitment domain-containing protein 9 (CARD9) immunity underlie deep dermatophytosis and invasive candidiasis.
They also indicate that CARD9 is important for preventing both mucosal and disseminated candidiasis, whereas the Th17 response is necessary for the defense against mucocutaneous candidiasis.
Although various degrees of T(H)17 dysfunction were also observed in most cases of isolated chronic mucocutaneous candidiasis, only in very few families was a distinct mutation detected (caspase recruitment domain family, member 9 [CARD9]), thus indicating certain forms of chronic mucocutaneous candidiasis as monogenic with a Mendelian pattern of inheritance.
Recent studies on patients with recurrent mucocutaneous candidiasis have led to the discovery of mutations in CARD9 and DECTIN-1, genes key to the production of the Th17-driving cytokines IL-1beta, IL-6, and IL-23.