ArticleArthritis & rheumatology (Hoboken, N.J.)2025
Comparative Analysis of Circulating and Synovial Immune Cells in Early Untreated Rheumatoid Arthritis and Their Relationship With Molecular Pathology and Disease Outcomes.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Beyond B cell helpers: diverse roles of peripheral helper T cells.International immunology · 2026Review
- Article
- Peripheral blood transcriptomic analysis of patients with rheumatoid arthritis associated interstitial lung disease reveals: distinct molecular signature with evidence of humoral and myeloid immunity.Arthritis research & therapy · 2026Article
- Predictive biomarkers for precision treatment in rheumatoid arthritis: are we there yet?Frontiers in pharmacology · 2026Review
- Immunological heterogeneity in rheumatoid arthritis: challenges in early-stage stratification, non-response to targeted therapy, and the restoration of immune tolerance.Frontiers in immunology · 2026Review
- Pathogenic Role of Cytokines in Rheumatoid Arthritis.Journal of clinical medicine · 2025Review
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Authors and funding
14 authors.
Funding
Abstract
objectiveTo assess the relationship of circulating and synovial immune cells with synovial molecular pathology and disease outcomes in patients with early rheumatoid arthritis (RA).
methodsPatients with early (<12 months) treatment-naive RA (n = 144) from the Pathobiology of Early Arthritis Cohort were included in this post hoc analysis. Following ultrasound (US)-guided synovial biopsy of the most active joint, patients received standard of care treatment and were observed for 12 months. Synovial biopsies were analyzed by immunohistochemistry and classified into synovial pathotypes. Peripheral blood (PB) samples (n = 70) underwent flow cytometry, whereas RNA sequencing from synovial tissue (n = 144) and matched PB (n = 55) were analyzed using signature-based deconvolution.
resultsT peripheral helper cells (Tph) cells, identified by flow cytometry, were the only circulating immune cell subset positively correlated with both systemic markers of inflammation (erythrocyte sedimentation rate and C-reactive protein) and local inflammation (US synovial thickening and synovitis score). Circulating Tph cells were also significantly higher in patients who were seropositive and patients with lymphomyeloid synovitis. Conversely, circulating B cells showed a significant inverse correlation with markers of inflammation, US scores, and disease activity. Signature-based deconvolution of matched synovial and PB identified divergent immune cell signatures. Although PB signatures showed no associations with longitudinal outcomes, synovium signatures were linked to clinical outcomes. In particular, patients achieving remission at six months (Disease Activity Score in 28 joints < 2.6) had higher baseline synovial Tph signatures and a greater posttreatment reduction of the Tph signature.
conclusionPatients with early untreated RA showed divergent immune cell signatures between synovia and PB. Tph cells, in both compartments, emerged as key markers for inflammation, disease activity, and treatment response.
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