Cartilage destruction in early rheumatoid arthritis patients correlates with CD21−/low double-negative B cells

Katrin Thorarinsdottir, Sarah McGrath, Kristina Forslind, Monica Leu Agelii, Anna Karin Hultgård Ekwall, Lennart T.H. Jacobsson, Anna Rudin, Inga Lill Mårtensson, Inger Gjertsson

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Involvement of B cells in the pathogenesis of rheumatoid arthritis (RA) is supported by the presence of disease-specific autoantibodies and the efficacy of treatment directed against B cells. B cells that express low levels of or lack the B cell receptor (BCR) co-receptor CD21, CD21−/low B cells, have been linked to autoimmune diseases, including RA. In this study, we characterized the CD21+ and CD21−/low B cell subsets in newly diagnosed, early RA (eRA) patients and investigated whether any of the B cell subsets were associated with autoantibody status, disease activity and/or joint destruction. Methods: Seventy-six eRA patients and 28 age- and sex-matched healthy donors were recruited. Multiple clinical parameters were assessed, including disease activity and radiographic joint destruction. B cell subsets were analysed in peripheral blood (PB) and synovial fluid (SF) using flow cytometry. Results: Compared to healthy donors, the eRA patients displayed an elevated frequency of naïve CD21+ B cells in PB. Amongst memory B cells, eRA patients had lower frequencies of the CD21+CD27+ subsets and CD21−/low CD27+IgD+ subset. The only B cell subset found to associate with clinical factors was the CD21−/low double-negative (DN, CD27IgD) cell population, linked with the joint space narrowing score, i.e. cartilage destruction. Moreover, in SF from patients with established RA, the CD21−/low DN B cells were expanded and these cells expressed receptor activator of the nuclear factor κB ligand (RANKL). Conclusions: Cartilage destruction in eRA patients was associated with an expanded proportion of CD21−/low DN B cells in PB. The subset was also expanded in SF from established RA patients and expressed RANKL. Taken together, our results suggest a role for CD21−/low DN in RA pathogenesis.

Original languageEnglish
Article number23
JournalArthritis Research and Therapy
Volume26
Issue number1
DOIs
Publication statusPublished - 2024 Dec

Subject classification (UKÄ)

  • Rheumatology and Autoimmunity

Free keywords

  • Cartilage destruction
  • CD21 DN B cells
  • Early rheumatoid arthritis

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