A Novel Interleukin 17 Receptor A Mutation in a Child with Chronic Mucocutaneous Candidiasis and Staphylococcal Skin Infections

Abstract

Objective: Chronic mucocutaneous candidiasis leads to persistent or recurrent fungal infections of the nail, skin, oral, and genital mucosa. Impaired interleukin 17-mediated immunity is a cause of chronic mucocutaneous candidiasis. We aimed to show the pathogenicity of a novel interleukin 17 receptor A mutation through functional studies.

Materials and methods: After next-generation sequencing analysis showed the interleukin 17 receptor A variant, we confirmed the variant by Sanger sequencing and functional validation of the variant by flow cytometry.

Results: We present the case of a 6-year-old male patient who presented with recurrent oral and genital Candida infections and eczema. He had staphylococcal skin lesions, fungal susceptibility, and eczema. The patient carried a novel homozygous nonsense [(c.787C> T) (p.Arg263Ter)] mutation in the interleukin 17 receptor A gene. Sanger sequencing confirmed the variant and revealed the segregation of the variant in the family. We used flow cytometry to detect interleukin 17 receptor A protein expression in peripheral blood mononuclear cells from patients and measured Th17 cell percentage. We observed low interleukin 17 receptor A protein expression in patient peripheral blood mononuclear cells, decreased CD4+ interleukin 17+ cell percentage, and decreased interleukin 17F expression in CD4+ cells compared to healthy controls.

Conclusions: Innate immune defects may lead to chronic recurrent fungal and bacterial infections of the skin, mucosa, and nails. Generally, genetic and functional analysis is needed in addition to basic immunological tests.

Figure 1.

(A) Pedigree (fraternal twins). (B) Schematic diagram of the mutations of the IL17RA protein detected to date, including our patient. Our patient is shown in red. (C) Sanger sequence analysis of IL-17RA mutation in patients and family members. While the patient was homozygous for the IL-17RA mutation [(c.787C> T) (p.Arg263Ter)], his parents and one sibling (healthy sibling 1) were heterozygous for the same mutation. No mutation was found in the patient’s twin (healthy sibling 3) and the other sibling (healthy sibling 2). IL17RA, interleukin 17 receptor A.

Figure 2.

(A) Purulent lesion at the edge of the mouth. (B-C) Purulent lesions on the fingertips. (D) Folliculitis in the axillary area.

Figure 3.

(A) Flow cytometric analysis of IL17RA expression in the patient (isotype control (blue), healthy control (green), patient (red)). (B) Proliferation analysis of the patients’ unstimulated (up) and stimulated T cells (below). (C) Analysis of Th17 cells. (D) IL17F expression in CD4+ cells in the healthy control and the patient. IL17F, interleukin 17F; IL17RA, interleukin 17 receptor A.

Figure 4.

Clinical Presentation of 24 Patients with IL17RA Deficiency (^*indicates our patient’s clinical presentation)^,