Abstract

To investigate immune dysregulation in the peripheral blood that contributes to the pre-rheumatoid arthritis (RA) stage of RA development in anti-citrullinated protein antibody (ACPA)+ individuals.Using 37 markers by mass cytometry, we investigated peripheral blood mononuclear cells (PBMCs) from ACPA+ at-risk individuals (ARI), ACPA+ early untreated RA patients, and ACPA- controls in the Tokyo Women's Medical University (TWMU) cohort (n = 17 in each group). Computational algorithms, FlowSOM and Optimized t-Distributed Stochastic Neighbor Embedding (opt-SNE), were employed to explore specific immunological differences between study groups. These findings were further evaluated, and longitudinal changes were explored, using flow cytometry and PBMCs from the USA-based Targeting Immune Responses for Prevention of RA (TIP-RA) cohort that included 11 ACPA+ individuals who later developed RA (pre-RA), of which 9 had post-RA diagnosis PBMCs (post-RA), and 11 ACPA- controls.HLA-DR+ Tph cells, activated regulatory T cells, PD-1hi CD8+ T cells, and CXCR5- CD11c- CD38+ naïve B cells were significantly expanded in PBMCs from ARI and early RA patients from the TWMU cohort. Expansion of HLA-DR+ Tph cells and CXCR5- CD11c- CD38+ naïve B cells was likewise found in both pre-RA and post-RA time points in the TIP-RA cohort.The expansion of HLA-DR+ Tph cells and CXCR5- CD11c- CD38+ naïve B cells in ACPA+ individuals, including those who developed inflammatory arthritis and classified RA, supports a key role of these cells in transition from pre-RA to classified RA. These findings may identify a new mechanistic target for treatment and prevention in RA.

View details for DOI 10.1002/art.42839

View details for PubMedID 38412870