Abstract

ObjectivesThis study aims to investigate if addition of fibroblast-stromal cell markers to a classification of synovial pathotypes improves their predictive value on clinical outcomes in rheumatoid arthritis (RA).MethodsActive RA patients with a knee needle synovial biopsy at baseline and finished 1-year follow-up were recruited from a real-world prospective cohort. Positive staining for CD20, CD38, CD3, CD68, CD31, and CD90 were scored semiquantitatively (0-4). The primary outcome was radiographic progression defined as a minimum increase of 0.5 units of the modified total Sharp score from baseline to 1 year.ResultsAmong 150 recruited RA patients, 123 (82%) had qualified synovial tissue. Higher scores of CD20+ B cells, sublining CD68+ macrophages, CD31+ endothelial cells, and CD90+ fibroblasts were associated with less decrease in disease activity and greater increase in radiographic progression. A new fibroblast-based classification of synovial pathotypes giving more priority to myeloid and stromal cells classified samples as myeloid-stromal (57.7%, 71/123), lymphoid (31.7%, 39/123), and paucicellular pathotypes (10.6%, 13/123). RA patients with myeloid-stromal pathotype showed the highest rate of radiographic progression (43.7% vs. 23.1% vs. 7.7%, p = 0.011), together with the lowest rate of Boolean remission at 3, 6, and 12 months. Baseline synovial myeloid-stromal pathotype independently predicted radiographic progression at 1 year (adjusted OR: 3.199, 95% confidence interval (95% CI): 1.278, 8.010). Similar results were obtained in a subgroup analysis of treatment-naive RA.ConclusionsThis novel fibroblast-based myeloid-stromal pathotype could predict radiographic progression at 1 year in active RA patients which may contribute to the shift of therapeutic decision in RA.

Highlights

  • Rheumatoid arthritis (RA) is a highly heterogeneous disease with variable functional prognosis, level of joint destruction, and response to therapy [1]

  • This study aims to investigate if addition of fibroblast-stromal cell markers to a classification of synovial pathotypes improves their predictive value on clinical outcomes in rheumatoid arthritis (RA)

  • Higher scores of CD20+ B cells, sublining CD68+ macrophages, CD31+ endothelial cells, and CD90+ fibroblasts were associated with less decrease in disease activity and greater increase in radiographic progression

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Summary

Introduction

Rheumatoid arthritis (RA) is a highly heterogeneous disease with variable functional prognosis, level of joint destruction, and response to therapy [1]. Treat-to-target strategy (T2T) targeting remission or low disease activity (LDA) is widely applied to RA treatment, resulting in better disease management and quality of life [2, 3]. There remains a huge unmet need in RA management under the real-life situation [1]. Studies have been done to explore predictive biomarkers for poor prognosis, including genetic background, serologic biomarkers, and early imaging findings [5,6,7]. Simple measures such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are not specific to joint disease and the predictive value seems unreliable [8]

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