Chronic Mucocutaneous Candidiasis in Humans with Inborn Errors of Interleukin-17 Immunity

TLDR

Chronic mucocutaneous candidiasis disease is marked by recurrent skin, nail, and mucosal infections with Candida albicans (and occasionally Staphylococcus aureus) in patients lacking other infectious or autoimmune disorders. The study identifies two genetic causes of CMCD: autosomal recessive IL‑17RA deficiency and autosomal dominant IL‑17F deficiency. Complete IL‑17RA loss abolishes IL‑17A/F signaling, while partial IL‑17F loss impairs but does not eliminate activity, demonstrating that IL‑17A and IL‑17F are essential yet largely redundant for mucocutaneous defense against *C.

Abstract

Chronic mucocutaneous candidiasis disease (CMCD) is characterized by recurrent or persistent infections of the skin, nails, and oral and genital mucosae caused by Candida albicans and, to a lesser extent, Staphylococcus aureus, in patients with no other infectious or autoimmune manifestations. We report two genetic etiologies of CMCD: autosomal recessive deficiency in the cytokine receptor, interleukin-17 receptor A (IL-17RA), and autosomal dominant deficiency of the cytokine interleukin-17F (IL-17F). IL-17RA deficiency is complete, abolishing cellular responses to IL-17A and IL-17F homo- and heterodimers. By contrast, IL-17F deficiency is partial, with mutant IL-17F-containing homo- and heterodimers displaying impaired, but not abolished, activity. These experiments of nature indicate that human IL-17A and IL-17F are essential for mucocutaneous immunity against C. albicans, but otherwise largely redundant.