Rheumatoid arthritis

Comparative Analysis of Circulating and Synovial Immune Cells in Early Untreated Rheumatoid Arthritis and Their Relationship With Molecular Pathology and Disease Outcomes

Arthritis RheumatolPublished Post hoc analysis of the Pathobiology of Early Arthritis Cohort

Authors' conclusion

Patients 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.

Study context

Population
Patients with early (<12 months) treatment-naive rheumatoid arthritis (RA) from the Pathobiology of Early Arthritis Cohort; standard of care treatment, observed for 12 monthsPeripheral blood (PB) flow cytometry n = 70
Participants
144 patients
Methodological detailsUltrasound (US)-guided synovial biopsy, flow cytometry, RNA sequencing with signature-based deconvolution
  • US-guided synovial biopsy
  • Flow cytometry
  • RNA sequencing with signature-based deconvolution

Primary result

As reported in the abstract

Circulating and synovial immune cells vs inflammation, synovial pathology and outcomes
  • Circulating Tph cells were the only circulating subset positively correlated with both systemic (ESR, CRP) and local inflammation (US synovial thickening, synovitis score)
  • Circulating Tph cells significantly higher in seropositive patients and in lymphomyeloid synovitis
  • Circulating B cells significantly inversely correlated with inflammation markers, US scores and disease activity
  • Deconvolution of matched synovial and PB identified divergent immune cell signatures
  • PB signatures showed no associations with longitudinal outcomes; synovium signatures were linked to clinical outcomes
  • Remission at 6 months (DAS28 < 2.6) associated with higher baseline synovial Tph signatures and greater posttreatment reduction of the Tph signature

Original publication

Comparative Analysis of Circulating and Synovial Immune Cells in Early Untreated Rheumatoid Arthritis and Their Relationship With Molecular Pathology and Disease Outcomes. Arthritis Rheumatol. Published 7 July 2025. doi:10.1002/art.43194

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