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THU0033 Age-associated b cells in early drug-naÏve rheumatoid arthritis patients
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  1. A.E. Anderson1,
  2. G. Vidal-Pedrola1,
  3. D. Scheel-Toellner2,
  4. A. Pratt1,
  5. A. Mellor3,
  6. J. Isaacs1
  1. 1Musculoskeletal Research Group, Newcastle University, Newcastle upon Tyne
  2. 2Centre for Translational Inflammation Research, University of Birmingham, Birmingham
  3. 3Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK

Abstract

Background Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterised by joint inflammation and bone destruction. The presence of autoantibodies, years before the clinical onset of disease, and the efficacy of Rituximab, a B-cell depleting therapy, highlight a pathogenic role for B cells. Different groups have recently identified a novel subset of B cells named age-associated B cells (ABCs). Studies in mice autoimmune models and patients suffering from autoimmune diseases described these cells as CD19high CD21- CD11c+. Moreover, a subset of synovial fluid B cells with low levels of CD21, expresses FcRL4 and produces the cytokine RANKL, which stimulates the differentiation and activation of osteoclasts. The ABCs found in peripheral blood could therefore be the precursors of this FcRL4 positive subset found in synovia.

Objectives We aimed to investigate the proportion and phenotype of peripheral blood ABCs in patients suffering from early drug naïve RA.

Methods Newly presenting patients, naïve to immunomodulatory treatment, were recruited from the Newcastle Early Arthritis Clinic, and followed until diagnoses were confirmed. B-cell subsets in peripheral blood were detected and phenotyped using flow cytometry.

Results Our work showed increased proportions of ABCs in seropositive RA compared to other inflammatory arthritis controls, highlighting a potential link between autoantibody production and ABCs. Moreover, patients with high disease activity had higher proportions of ABCs in peripheral blood. Interestingly, the FcRL4+, the proliferating Ki67+ and the T-bet expressing B cells were enriched in the ABC population compared to the other B cell subsets. Furthermore, ABCs expressed high levels of MHC class II and co-stimulatory molecules, as well as the activation marker, CD69.

Conclusions These data supports a possible pathogenic role of ABCs in RA, potentially via autoantibody and T cell stimulatory ability, but further characterisation of this subset and functional studies are needed.

Disclosure of Interest None declared

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