1. Systemic inflammation and lymphocyte activation precede rheumatoid arthritis.
- Author
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He Z, Glass MC, Venkatesan P, Feser ML, Lazaro L, Okada LY, Tran NTT, He YD, Zaim SR, Bennett CE, Ravisankar P, Dornisch EM, Arishi NA, Asamoah AG, Barzideh S, Becker LA, Bemis EA, Buckner JH, Collora CE, Criley MAL, Demoruelle MK, Fleischer CL, Garber J, Genge PC, Gong Q, Graybuck LT, Gustafson CE, Hattel BC, Hernandez V, Heubeck AT, Kawelo EK, Krishnan U, Kuan EL, Kuhn KA, LaFrance CM, Lee KJ, Li R, Lord C, Mettey RR, Moss L, Musgrove B, Nguyen K, Ochoa A, Parthasarathy V, Pebworth MP, Pedrick C, Peng T, Phalen CG, Reading J, Roll CR, Seifert JA, Siedschlag MD, Speake C, Striebich CC, Stuckey TJ, Swanson EG, Takada H, Thai T, Thomson ZJ, Trieu N, Tsaltskan V, Wang W, Weiss MDA, Westermann A, Zhang F, Boyle DL, Goldrath AW, Bumol TF, Li XJ, Holers VM, Skene PJ, Savage AK, Firestein GS, Deane KD, Torgerson TR, and Gillespie MA
- 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. We provide a suite of tools at https://apps.allenimmunology.org/aifi/insights/ra-progression/ to facilitate exploration and enhance accessibility of this extensive dataset.
- Published
- 2024
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