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Nat Commun ; 15(1): 4991, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862501

RESUMEN

Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function. CD8 + T cells show higher oligoclonality than CD4 + T cells, with the largest synovial clones enriched in GZMK+ cells. CD8 + T cells with possibly virus-reactive TCRs are distributed across transcriptomic clusters. In the B cell compartment, NR4A1+ activated B cells, and plasma cells are enriched in the synovium and demonstrate substantial clonal expansion. We identify synovial plasma cells that share BCRs with synovial ABC, memory, and activated B cells. Receptor-ligand analysis predicted IFNG and TNFRSF members as mediators of synovial Tph-B cell interactions. Together, these results reveal clonal relationships between functionally distinct lymphocyte populations that infiltrate the synovium of patients with RA.


Asunto(s)
Artritis Reumatoide , Linfocitos B , Membrana Sinovial , Humanos , Artritis Reumatoide/inmunología , Artritis Reumatoide/metabolismo , Artritis Reumatoide/genética , Artritis Reumatoide/patología , Membrana Sinovial/inmunología , Membrana Sinovial/metabolismo , Linfocitos B/inmunología , Linfocitos B/metabolismo , Femenino , Masculino , Persona de Mediana Edad , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Subgrupos Linfocitarios/inmunología , Subgrupos Linfocitarios/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Análisis de la Célula Individual , Transcriptoma , Células Plasmáticas/inmunología , Células Plasmáticas/metabolismo , Anciano , Activación de Linfocitos , Adulto
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