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

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.

Figure 1.

High titers of auto-Abs against IFN-α, IL-17A, IL-17F, and IL-22 in the plasma from patients with APS-I. Anti–IFN-α, –IL-17A, –IL-17F, and –IL-22 circulating IgG titers were measured by multiplex particle-based flow cytometry in 33 samples from patients with APS-I and in 37 samples from healthy controls. FI is plotted on the y axis. Representative data for two experiments are shown.

Figure 2.

Specific auto-Abs against IL-17A, IL-17F, and/or IL-22 in the plasma from patients with APS-I. Western blot against rIL-17A, rIL-17F, rIL-22, and rIL-23 were performed using plasma from a healthy individual or from five patients with APS-I, diluted 1:500. Representative data for three experiments are shown. Dashed lines indicate that intervening lanes have been spliced out.

Figure 3.

Neutralizing auto-Abs against IL-17A in the plasma from a patient with APS-I. IL-6 production, after 48 h of stimulation with 50 ng/ml IL-17A, by control SV-40–transformed fibroblasts incubated with 10% plasma from two controls or from one patient (APS-I patient 7; means and errors bars from duplicates are shown). The data shown are representative of two experiments.