Interferon-driven gene signature identifies two distinct subgroups in rheumatoid factor-positive polyarticular juvenile idiopathic arthritis

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ID: 328264
2026
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Abstract
OBJECTIVE: To characterize the demographic, clinical, serological, genetic background, course and value of the interferon (IFN)-score in a cohort of patients with rheumatoid factor (RF)-positive polyarticular juvenile idiopathic arthritis (pJIA). METHODS: Monocentric retrospective study of patients with RF-positive pJIA. Demographic, clinical and laboratory data were collected. The IFN-score was calculated based on the expression levels of 24 IFN stimulated genes. Whole exome sequencing was performed in 22 patients. RESULTS: Thirty-two patients were included. The IFN score was positive in 18 patients (56.2%) and negative in 14 patients (43.7%). An increased IFN score was associated with a significantly higher family history of autoimmunity (p = 0.0004), parental first-degree consanguinity (p = 0.05) and prevalence of antibodies to anti-cyclic citrullinated peptide (ACPA) (p = 0.01). Three patients with interstitial lung disease exhibited a positive IFN score. Conversely, demographic features and characteristics of polyarthritis did not differ between the two groups. Clinically inactive disease was achieved in 21/32 (66%) patients, with no significant difference according to the IFN score. Remission was never achieved with methotrexate alone. We identified one patient with a pathogenic de novo mutation in COPA. Additionally, ultra-rare variants in genes related to IFN and/or innate immunity were found in 21/22 (95.5%) patients. CONCLUSION: The IFN signature identified two distinct subgroups in RF-positive pJIA according to family history and immunological features. Our study suggests that patients with an elevated IFN score should be screened for pulmonary involvement. Future prospective studies are required to validate the use of the IFN score as a biomarker in RF-positive pJIA.
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Authors Anna Agrusti, C. David, Sylvain Breton, Isabelle Melki, Pierre Quartier, Cécile Dumaine, Héloïse Reumaux, A.-L. Jurquet, Benjamin Fournier, Luís Seabra, Gillian I Rice, Brigitte Bader-Meunier, Marie-Louise Frémond
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Journal Lara D. Veeken
Year 2026
DOI
10.1093/rheumatology/keag486
URL
https://doi.org/10.1093/rheumatology/keag486
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