Clinical utility of measuring CD4+ T follicular cells in patients with immune dysregulation

Brenna LaBere; Alan A Nguyen; Saddiq B Habiballah; Megan Elkins; Juliet Imperial; Betty Li; Sridevi Devana; Suraj Timilsina; Spencer B Stubbs; Jill Joerger; Janet Chou; Craig D Platt

doi:10.1016/j.jaut.2023.103088

Clinical utility of measuring CD4⁺ T follicular cells in patients with immune dysregulation

J Autoimmun. 2023 Aug 5:140:103088. doi: 10.1016/j.jaut.2023.103088. Online ahead of print.

Authors

Affiliations

¹ Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
² Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
³ Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Takeda, Cambridge, MA, USA.
⁵ Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: craig.platt@childrens.harvard.edu.

PMID: 37549449
PMCID: PMC10839119 (available on 2025-02-05)
DOI: 10.1016/j.jaut.2023.103088

Abstract

Mechanistic studies of autoimmune disorders have identified circulating T follicular helper (cTfh) cells as drivers of autoimmunity. However, the quantification of cTfh cells is not yet used in clinical practice due to the lack of age-stratified normal ranges and the unknown sensitivity and specificity of this test for autoimmunity. We enrolled 238 healthy participants and 130 patients with common and rare disorders of autoimmunity or autoinflammation. Patients with infections, active malignancy, or any history of transplantation were excluded. In 238 healthy controls, median cTfh percentages (range 4.8%-6.2%) were comparable among age groups, sexes, races, and ethnicities, apart from a significantly lower percentages in children less than 1 year of age (median 2.1%, CI: 0.4%-6.8, p < 0.0001). Among 130 patients with over 40 immune regulatory disorders, a cTfh percentage exceeding 12% had 88% sensitivity and 94% specificity for differentiating disorders with adaptive immune cell dysregulation from those with predominantly innate cell defects. This threshold had a sensitivity of 86% and specificity of 100% for active autoimmunity and normalized with effective treatment. cTfh percentages exceeding 12% distinguish autoimmunity from autoinflammation, thereby differentiating two endotypes of immune dysregulation with overlapping symptoms and different therapies.

Keywords: Autoimmunity; Evans syndrome; Immune dysregulation; Primary immune regulatory disorder; T follicular helper cells.

Abstract

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