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