biostudies-literatureUnknownHe ZNIAMS NIH HHSSome 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 subioRxiv : the preprint server for biology2024.10.25.620344https://www.ebi.ac.uk/biostudies/studies/S-EPMC11565773biostudies-literatureSystemic inflammation and lymphocyte activation precede rheumatoid arthritis.PMC11565773P30 AR079369Zhang FAsamoah AGMettey RRZaim SRPeng TGraybuck LTReading JLi XJSwanson EGParthasarathy VGarber JOchoa ACollora CEGenge PCKuan ELFeser MLBoyle DLWang WVenkatesan PFirestein GSGillespie MARoll CROkada LYKrishnan UHeubeck ATFleischer CLLi RGoldrath AWWestermann ALaFrance CMTsaltskan VSavage AKTakada HHe ZHattel BCHolers VMBecker LABuckner JHGong QStuckey TJRavisankar PHe YDSpeake CThai TStriebich CCTorgerson TRPedrick CDemoruelle MKPebworth MPBarzideh SGustafson CEHernandez VKuhn KATrieu NSeifert JASkene PJDeane KDSiedschlag MDMusgrove BThomson ZJArishi NANguyen KWeiss MDABennett CEBumol TFDornisch EMLazaro LTran NTTBemis EAGlass MCLord CMoss LKawelo EKLee KJCriley MALPhalen CGfalseSystemic inflammation and lymphocyte activation precede rheumatoid arthritis.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 su2024-01-01T00:00:00Z2024 Nov2026-05-28T03:25:37.563Z2025-04-04T02:47:47.154ZS-EPMC115657733955404210.1101/2024.10.25.620344