Disordered T cell-B cell interactions in autoantibody-positive inflammatory arthritis.

T peripheral helper (Tph) cells, identified in the synovium of adults with seropositive rheumatoid arthritis, drive B cell maturation and antibody production in non-lymphoid tissues. We sought to determine if similarly dysregulated T cell-B cell interactions underlie another form of inflammatory arthritis, juvenile oligoarthritis (oligo JIA). Clonally expanded Tph cells able to promote B cell antibody production preferentially accumulated in the synovial fluid (SF) of oligo JIA patients with antinuclear antibodies (ANA) compared to autoantibody-negative patients. Single-cell transcriptomics enabled further definition of the Tph gene signature in inflamed tissues and showed that Tph cells from ANA-positive patients upregulated genes associated with B cell help to a greater extent than patients without autoantibodies. T cells that co-expressed regulatory T and B cell-help factors were identified. The phenotype of these Tph-like Treg cells suggests an ability to restrain T cell-B cell interactions in tissues. Our findings support the central role of disordered T cell-help to B cells in autoantibody-positive arthritides.

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Copyright © 2023 Julé, Lam, Taylor, Hoyt, Wei, Gutierrez-Arcelus, Case, Chandler, Chang, Cohen, Dedeoglu, Halyabar, Hausmann, Hazen, Janssen, Lo, Lo, Meidan, Roberts, Wobma, Son, Sundel, Lee, Sage, Chatila, Nigrovic, Rao and Henderson.

Déclaration de conflit d'intérêts

PN has been supported by investigator-initiated research grants from Bristol-Myers Squibb BMS and Pfizer; consulting from BMS, Cerecor, Miach Orthopedics, Novartis, Pfizer, Quench Bio, Sigilon, Simcere, Sobi, and XBiotech; royalties from UpToDate Inc and the American Academy of Pediatrics.; and salary support from CARRA. DR reports personal fees from Pfizer, Janssen, Merck, Scipher Medicine, GlaxoSmithKline, and BMS and grant support from Janssen, Merck, and BMS, outside the submitted work. DR is a co-inventor on a patent application on Tph cells. LH has received salary support from CARRA; consulting fees from Sobi, Pfizer, and Adaptive Biotechnologies; and investigator-initiated research grants from Bristol-Myers Squibb. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.