Chronic mucocutaneous candidiasis: characterization of a family with STAT-1 gain-of-function and development of an ex-vivo assay for Th17 deficiency of diagnostic utility

• DOI: 10.1111/cei.12746
• Publication Date: 2015-12-01T07:05:43Z
• Authors: F Dhalla; H Fox; E E Davenport; R Sadler; C Anzilotti; P A van Schouwenburg; B Ferry; H Chapel; J C Knight; S Y Patel
• Keywords: Chronic mucocutaneous candidiasis; Ex vivo; Mucocutaneous zone

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