Decreased IL-17-producing T(H) cells as a diagnostic marker for STAT signaling-related primary immunodeficiencies
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Authors
Molnár, Emese
Kovács, Gábor
Tahami, Fariba
Andrikovics, Hajnalka
Burns, Siobhan
Grigoriadou, Sofia
Buckland, Matthew
Gilmour, Kimberly
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Issue Date
2026
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Abstract
BACKGROUND: Certain primary immunodeficiencies present with decreased T(H)17 counts, including signal transducer and activator of transcription 3 (STAT3)- and dedicator of cytokinesis 8 (DOCK8)-linked hyper-IgE syndrome (HIES) and STAT1-linked chronic mucocutaneous candidiasis disease (CMCD). The diagnosis of CMCD and HIES relies on clinical features and molecular genetics. OBJECTIVE: We sought to evaluate the diagnostic use of T(H)17% in patients suspected of HIES or CMCD. METHODS: A total of 160 patient samples assessed for T(H)17% at Great Ormond Street Hospital National Health Service Foundation Trust for Children, London, between 2019 and 2022 were included in this cohort. Among them, 94 patients exhibited low T(H)17% (<0.4%). Sufficient clinical and molecular data were available for 52 patients. Clinical data, molecular genetic results, and National Institutes of Health-HIES scores were analyzed. RESULTS: From the 52 evaluable patients with a low T(H)17%, 27 (51.92%) harbored pathogenic or likely pathogenic (P/LP) variants in the genes STAT1 (n = 8), STAT3 (n = 12), DOCK8 (n = 6), and autoimmune regulator (AIRE ) (n = 1). In contrast, no disease-causing variants in these genes were identified in patients with a normal T(H)17% (n = 58). From the scoring parameters, elevated IgE levels (P = .0008), pneumonia (P = .0200), and pathological fractures (P = .0622) were associated with a diagnosis of HIES. CONCLUSIONS: T(H)17 measurement demonstrated high sensitivity for detecting P/LP variants of STAT3, DOCK8, or STAT1. Although T(H)17 measurement is a valuable screening tool for excluding patients with P/LP variants in these genes, molecular genetics remains essential for a definitive diagnosis.
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The journal of allergy and clinical immunology.Global
Volume
5
Issue
2