Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent and persistent superficial infections, with Candida albicans affecting the mucous membranes, skin and nails. It can be acquired or caused by primary immune deficiencies, particularly those that impair interleukin (IL)-17 and IL-22 immunity. We describe a single kindred with CMC and the identification of a STAT1 GOF mutation by whole exome sequencing (WES). We show how detailed clinical and immunological phenotyping of this family in the context of WES has enabled revision of disease status and clinical management. Together with analysis of other CMC cases within our cohort of patients, we used knowledge arising from the characterization of this family to develop a rapid ex-vivo screening assay for the detection of T helper type 17 (Th17) deficiency better suited to the routine diagnostic setting than established in-vitro techniques, such as intracellular cytokine staining and enzyme-linked immunosorbent assay (ELISA) using cell culture supernatants. We demonstrate that cell surface staining of unstimulated whole blood for CCR6⁺ CXCR3⁻ CCR4⁺ CD161⁺ T helper cells generates results that correlate with intracellular cytokine staining for IL-17A, and is able to discriminate between patients with molecularly defined CMC and healthy controls with 100% sensitivity and specificity within the cohort tested. Furthermore, removal of CCR4 and CD161 from the antibody staining panel did not affect assay performance, suggesting that the enumeration of CCR6⁺ CXCR3⁻ CD4⁺ T cells is sufficient for screening for Th17 deficiency in patients with CMC and could be used to guide further investigation aimed at identifying the underlying molecular cause.

Original publication

DOI

10.1111/cei.12746

Type

Journal article

Journal

Clin Exp Immunol

Publication Date

05/2016

Volume

184

Pages

216 - 227

Keywords

Th17, chemokine receptors, chronic mucocutaneous candidiasis, surface phenotyping, Adolescent, Adult, Base Sequence, CD4 Antigens, Candida albicans, Candidiasis, Chronic Mucocutaneous, Child, Child, Preschool, Enzyme-Linked Immunosorbent Assay, Exome, Family, Female, Humans, Infant, Interleukin-17, Male, Middle Aged, Mucous Membrane, Receptors, CCR6, Receptors, CXCR3, STAT1 Transcription Factor, Sequence Analysis, DNA, Staining and Labeling, Th17 Cells, Young Adult