Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I

TLDR

Patients with APS‑I commonly develop chronic mucocutaneous candidiasis. The study aimed to determine whether CMC in APS‑I is caused by autoantibodies against IL‑17 cytokines. All 33 APS‑I patients had specific, neutralizing autoantibodies to IL‑17A, IL‑17F, and IL‑22, absent in healthy controls and other autoimmune diseases, suggesting these antibodies drive CMC.

Abstract

Most patients with autoimmune polyendocrine syndrome type I (APS-I) display chronic mucocutaneous candidiasis (CMC). We hypothesized that this CMC might result from autoimmunity to interleukin (IL)-17 cytokines. We found high titers of autoantibodies (auto-Abs) against IL-17A, IL-17F, and/or IL-22 in the sera of all 33 patients tested, as detected by multiplex particle-based flow cytometry. The auto-Abs against IL-17A, IL-17F, and IL-22 were specific in the five patients tested, as shown by Western blotting. The auto-Abs against IL-17A were neutralizing in the only patient tested, as shown by bioassays of IL-17A activity. None of the 37 healthy controls and none of the 103 patients with other autoimmune disorders tested had such auto-Abs. None of the patients with APS-I had auto-Abs against cytokines previously shown to cause other well-defined clinical syndromes in other patients (IL-6, interferon [IFN]-gamma, or granulocyte/macrophage colony-stimulating factor) or against other cytokines (IL-1beta, IL-10, IL-12, IL-18, IL-21, IL-23, IL-26, IFN-beta, tumor necrosis factor [alpha], or transforming growth factor beta). These findings suggest that auto-Abs against IL-17A, IL-17F, and IL-22 may cause CMC in patients with APS-I.