Addition of Fibroblast-Stromal Cell Markers to Immune Synovium Pathotypes Better Predicts Radiographic Progression at 1 Year in Active Rheumatoid Arthritis

• Published in: Frontiers in immunology Vol. 12; p. 778480
• Main Authors: Zhang, Xue-Pei, Ma, Jian-Da, Mo, Ying-Qian, Jing, Jun, Zheng, Dong-Hui, Chen, Le-Feng, Wu, Tao, Chen, Chu-Tao, Zhang, Qian, Zou, Yao-Yao, Lin, Jian-Zi, Xu, Yan-Hui, Zou, Yao-Wei, Yang, Ze-Hong, Ling, Li, Miossec, Pierre, Dai, Lie
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 23.11.2021
• Subjects: Adult; Antigens, CD - analysis; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - diagnostic imaging; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - pathology; Biomarkers - analysis; Biopsy, Needle; Disease Progression; Female; Fibroblasts - drug effects; Fibroblasts - immunology; Fibroblasts - pathology; Humans; Immunohistochemistry; Immunology; Knee Joint - diagnostic imaging; Knee Joint - drug effects; Knee Joint - immunology; Knee Joint - pathology; Male; Middle Aged; myeloid-stromal pathotype; Predictive Value of Tests; Prospective Studies; radiographic progression; Remission Induction; rheumatoid arthritis; stromal cells; Stromal Cells - drug effects; Stromal Cells - immunology; Stromal Cells - pathology; Synovial Membrane - diagnostic imaging; Synovial Membrane - drug effects; Synovial Membrane - immunology; Synovial Membrane - pathology; synovial tissue; Time Factors; Treatment Outcome; myeloid-stromal pathotype; radiographic progression; stromal cells; rheumatoid arthritis; synovial tissue
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.778480

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). Active 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. Among 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%, = 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. This 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.