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Clinically validated assay for rapid determination of type I and type II interferon activity in systemic inflammatory diseases.

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The Journal of allergy and clinical immunology 2026
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Lam MT, Basu A, Brodeur KE, LeSon CE, Hsu EE, Alhezam MA

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[BACKGROUND] Type I interferons (IFN-I) and type II interferon (IFN-γ) contribute to the pathogenesis of inflammatory diseases, but measurement of these cytokines remains challenging in the clinical s

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APA Lam MT, Basu A, et al. (2026). Clinically validated assay for rapid determination of type I and type II interferon activity in systemic inflammatory diseases.. The Journal of allergy and clinical immunology. https://doi.org/10.1016/j.jaci.2026.01.021
MLA Lam MT, et al.. "Clinically validated assay for rapid determination of type I and type II interferon activity in systemic inflammatory diseases.." The Journal of allergy and clinical immunology, 2026.
PMID 41638262 ↗

Abstract

[BACKGROUND] Type I interferons (IFN-I) and type II interferon (IFN-γ) contribute to the pathogenesis of inflammatory diseases, but measurement of these cytokines remains challenging in the clinical setting.

[OBJECTIVE] We aimed to develop a clinical test that rapidly captures the activity of IFN-I and IFN-γ.

[METHODS] We compared RNA sequencing data from healthy controls and patients with macrophage activation syndrome, multisystem inflammatory syndrome in children, and systemic lupus erythematosus to evaluate biomarkers of IFN-I and IFN-γ signaling. We utilized a flow cytometry assay to measure interferon-inducible markers. The findings were verified by a clinical laboratory that independently developed and validated this assay.

[RESULTS] We identified CD274 (programmed death ligand 1, or PD-L1) as a biomarker of IFN-γ signaling and confirmed CD169 (SIGLEC-1) as a readout of IFN-I activity. We utilized a flow cytometry assay to quantify CD169 and CD274 expression on monocytes and demonstrated the validity of this method for rapid screening of interferon dysregulation in patients with various inflammatory diseases including, among others, macrophage activation syndrome, hemophagocytic lymphohistiocytosis, multisystem inflammatory syndrome in children, systemic lupus erythematosus, juvenile idiopathic arthritis, and juvenile dermatomyositis. We further demonstrated the utility of this test for assessment of interferon dysregulation in monogenic inflammatory diseases and for efficacy monitoring of medications that target the interferon pathways including Janus kinase inhibitors, emapalumab, and anifrolumab. Finally, we outlined the steps of assay validation and clinical implementation, and we showed reproducible findings in a clinical laboratory.

[CONCLUSION] Flow cytometry analysis of CD169 and CD274 is an effective method to rapidly quantify IFN-I and IFN-γ activity in the clinical setting.

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