Decreased IL-17–producing TH cells as a diagnostic marker for STAT signaling-related primary immunodeficiencies

Q: Which primary immunodeficiencies are associated with decreased TH17 counts in this study?

The study focuses on STAT3- and DOCK8-linked hyper-IgE syndrome (HIES) and STAT1-linked chronic mucocutaneous candidiasis disease (CMCD).

Q: How many patient samples were evaluated, and how many showed low TH17%?

A total of 160 samples were assessed for TH17% between 2019 and 2022, and 94 patients exhibited low TH17% (<0.4%).

Q: Is TH17 measurement sufficient for definitive diagnosis?

TH17 measurement showed high sensitivity for detecting pathogenic/likely pathogenic variants in STAT3, DOCK8, or STAT1. However, molecular genetics remains essential for a definitive diagnosis.

Sep 29, 2026

Upload by Guten tag

Decreased IL-17–producing T helper (TH17) cell counts occur in specific primary immunodeficiencies, particularly STAT3- and DOCK8-linked hyper-IgE syndrome and STAT1-linked chronic mucocutaneous candidiasis disease. A cohort of 160 samples assessed TH17% between 2019 and 2022, with 94 showing low TH17% and 52 having adequate clinical and molecular data. Among evaluable low-TH17% patients, 51.92% carried pathogenic or likely pathogenic variants in STAT1, STAT3, DOCK8, or AIRE. Elevated IgE, pneumonia, and pathological fractures supported HIES diagnosis; TH17 measurement showed high sensitivity, but molecular genetics remained essential for definitive diagnosis.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Background

Objective

Methods

Cohort and testing

Statistical associations

Results

Conclusions

Decreased IL-17–producing TH cells as a diagnostic marker for STAT signaling–related primary immunodeficiencies Emese Molnr, MD, PhD,a, b,c Gbor Kovcs, MD,d Fariba Tahami, MSc,a Hajnalka Andrikovics, MD, PhD,c,e Siobhan Burns, MD, PhD,f Sofia Grigoriadou, MD, PhD,b Matthew Buckland, MD, PhD,a, b and Kimberly Gilmour, PhDa London, United Kingdom; and Budapest, Hungary Background: Certain primary immunodeficiencies present with decreased TH17 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 TH17% in patients suspected of HIES or CMCD. Methods: A total of 160 patient samples assessed for TH17% 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 TH17%(<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 TH17%, 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 inpatients with a normal TH17%(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: TH17 measurement demonstrated high sensitivity for detecting P/LP variants of STAT3, DOCK8, or STAT1. Although TH17 measurement is a valuable screening tool for excluding patients with P/LP variants in these genes, molecular genetics remains essential for a definitive diagnosis. (J Allergy Clin Immunol Global 2026;5:100603.) Key words: IgE, TH17, hyper-IgE syndrome, STAT1, STAT3, DOCK8, CMCD From athe Laboratory of Immunology and Cellular Therapy, Great Ormond Street Hospital for Children, NHS Foundation Trust, and bBarts Health NHS Trust, London; the Departments of cTransfusion Medicine and dPhysiology, Semmelweis University, and ethe Laboratory of Molecular Genetics, Central Hospital of Southern Pest, Budapest; and fRoyal Free London NHS Trust, London. Received for publication April 11, 2025; revised August 17, 2025; accepted for publication September 1, 2025. Available online November 13, 2025. Corresponding author: Kimberly C. Gilmour, PhD, Camelia Botnar Laboratories, Level 4, Great Ormond Street Hospital for Children, NHS Foundation Trust, Great Ormond Street, London WC1N 3JH, [UK. E-mail:](UK. E-mail: Kimberly.Gilmour@gosh.nhs.uk)[ Kimberly.Gilmour@gosh.nhs.uk](UK. E-mail: Kimberly.Gilmour@gosh.nhs.uk). The CrossMark symbol notifies online readers when updates have been made to the article such as errata or minor corrections 2772-8293/$36.00 © 2025 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY-NCND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)) . [https://doi.org/10.1016/j.jacig.2025.100603](https://doi.org/10.1016/j.jacig.2025.100603) Abbreviations used ACMG: American College of Medical Genetics and Genomics AD-HIES: Autosomal-dominant hyper-IgE syndrome AIRE: Autoimmune regulator CMCD: Chronic mucocutaneous candidiasis DOCK8: Dedicator of cytokinesis 8 gnomAD: Genome Aggregation Database HIES: Hyper-IgE syndrome NIH: National Institutes of Health P/LP: Pathogenic or likely pathogenic STAT1/STAT3: Signal transducer and activator of tran

FAQs

Which primary immunodeficiencies are associated with decreased TH17 counts in this study?

The study focuses on STAT3- and DOCK8-linked hyper-IgE syndrome (HIES) and STAT1-linked chronic mucocutaneous candidiasis disease (CMCD).

How many patient samples were evaluated, and how many showed low TH17%?

A total of 160 samples were assessed for TH17% between 2019 and 2022, and 94 patients exhibited low TH17% (<0.4%).

Is TH17 measurement sufficient for definitive diagnosis?

TH17 measurement showed high sensitivity for detecting pathogenic/likely pathogenic variants in STAT3, DOCK8, or STAT1. However, molecular genetics remains essential for a definitive diagnosis.

Sep 29, 2026

Upload by Guten tag