Nature communications · 2024
Clonal associations between lymphocyte subsets and functional states in rheumatoid arthritis synovium.
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Dunlap Garrett, Wagner Aaron, Meednu Nida, Wang Ruoqiao, Zhang Fan, Ekabe Jabea Cyril, Jonsson Anna Helena, Wei Kevin, Sakaue Saori, Nathan Aparna, Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network, Bykerk Vivian P, Donlin Laura T, Goodman Susan M, Firestein Gary S, Boyle David L, Holers V Michael, Moreland Larry W, Tabechian Darren, Pitzalis Costantino, Filer Andrew, Raychaudhuri Soumya, Brenner Michael B, Thakar Juilee, McDavid Andrew, Rao Deepak A, Anolik Jennifer H
Аннотация
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.