Triaille, Clement;
Vansteenkiste, Louise;
Constant, Manuel;
Ambroise, Jérôme;
Méric de Bellefon, Laurent;
Nzeusseu Toukap, Adrien;
Sokolova, Tatiana;
Galant, Christine;
Coulie, Pierre;
Carrasco, Javier;
Durez, Patrick;
Lauwerys, Bernard R.
Paired Rheumatoid Arthritis Synovial Biopsies From Small and Large Joints Show Similar Global Transcriptomic Patterns With Enrichment of Private Specificity TCRB and TCR Signaling Pathways
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Medientyp:
E-Artikel
Titel:
Paired Rheumatoid Arthritis Synovial Biopsies From Small and Large Joints Show Similar Global Transcriptomic Patterns With Enrichment of Private Specificity TCRB and TCR Signaling Pathways
Beteiligte:
Triaille, Clement;
Vansteenkiste, Louise;
Constant, Manuel;
Ambroise, Jérôme;
Méric de Bellefon, Laurent;
Nzeusseu Toukap, Adrien;
Sokolova, Tatiana;
Galant, Christine;
Coulie, Pierre;
Carrasco, Javier;
Durez, Patrick;
Lauwerys, Bernard R.
Beschreibung:
<jats:sec><jats:title>Objectives</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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. <jats:italic>TCRB</jats:italic> variable sequences were obtained from synovial and blood RNA samples.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec>