Paired Rheumatoid Arthritis Synovial Biopsies From Small and Large Joints Show Similar Global Transcriptomic Patterns With Enrichment of Private Specificity and TCR Signaling Pathways.
(2020) Frontiers in Immunology — Vol. 11, p. 593083 [1-9] (2020)
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- (en) OBJECTIVES: We explored histological and transcriptomic profiles of paired synovial biopsies from rheumatoid arthritis (RA) patients, in order to assess homogeneity in synovial tissue at the individual level. METHODS: Synovial biopsies were performed simultaneously in one small and one large joint per patient using needle-arthroscopy for the knee and ultrasound-guided biopsy for the hand or wrist. Synovium from individuals with osteoarthritis was used as controls. Paraffin-embedded samples were stained for CD3, CD20, and CD68. Total RNA was hybridized on high-density microarrays. TCRB variable sequences were obtained from synovial and blood RNA samples. RESULTS: Twenty paired biopsies from 10 RA patients with active disease were analyzed. Semi-quantification of histological markers showed a positive correlation for synovial hyperplasia, inflammatory infiltrates and CD3-positive T cells between pairs. Pairwise comparison of transcriptomic profiles showed similar expression of RA-related molecular pathways (TCR signaling, T cell costimulation and response to TNFα). T cells clonotypes were enriched in all but one joints compared to blood, regardless of the magnitude of T cell infiltration. Enriched clonotypes were shared between pairs (23-100%), but this was less the case in pairs of joints displaying weaker T cell signatures and more pronounced germinal center-like transcriptomic profiles. CONCLUSION: Cellular and molecular alterations in RA synovitis are similar between small and large joints from the same patient. Interindividual differences in magnitude of T cell infiltrates and distribution of enriched T cell clonotypes support the concept of distinct synovial pathotypes in RA that are associated with systemic versus local antigen-driven activation of T cells.
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Triaille, C., Vansteenkiste, L., Constant, M., Ambroise, J., Méric de Bellefon, L., Nzeusseu Toukap, A., Sokolova, T., Galant, C., Coulie, P., Carrasco, J., Durez, P., & Lauwerys, B. (2020). Paired Rheumatoid Arthritis Synovial Biopsies From Small and Large Joints Show Similar Global Transcriptomic Patterns With Enrichment of Private Specificity and TCR Signaling Pathways. Frontiers in Immunology, 11, 593083 [1-9]. https://doi.org/10.3389/fimmu.2020.593083 (Original work published 2020)