Systemic inflammation and lymphocyte activation precede rheumatoid arthritis
Abstract
Some autoimmune diseases, including rheumatoid arthritis (RA), are preceded by a critical subclinical phase of disease activity. Proactive clinical management is hampered by a lack of biological understanding of this subclinical "at-risk" state and the changes underlying disease development. In a cross-sectional and longitudinal multi-omics study of peripheral immunity in the autoantibody-positive at-risk for RA period, we identified systemic inflammation, proinflammatory-skewed B cells, expanded Tfh17-like cells, epigenetic bias in naive T cells, TNF+IL1B+ monocytes resembling a synovial macrophage population, and CD4 T cell transcriptional features resembling those suppressed by abatacept (CTLA4-Ig) in RA patients. Our findings characterize pathogenesis prior to clinical diagnosis and suggest the at-risk state exhibits substantial immune alterations that could potentially be targeted for early intervention to delay or prevent autoimmunity.
Competing Interest Statement
KDD has received honorarium and reduced-cost biomarker assays from Werfen. KDD and MKD receive grant funding from Gilead Sciences. GSF, LYO, NTT, YH, CEB, XL and TRT receive grant funding from Eli Lilly. AWG serves on the scientific advisory boards of Arsenal Bio and Foundery Innovations and is a cofounder of TCura.
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