Journal Article

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

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

2024

Overview

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, CD27 − IgD − ) 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Arthritis, Rheumatoid - pathology / Articular cartilage / Autoantibodies / Autoimmunitet och inflammation / Autoimmunity and Inflammation / B cells / B-Lymphocyte Subsets / B-Lymphocytes / Cartilage / Cartilage - pathology / Cartilage destruction / CD21 DN B cells −/low / CD21−/low DN B cells / Clinical Medicine / Complement receptors / Complications and side effects / Degeneration (Pathology) / Development and progression / Discriminant analysis / Disease / Early rheumatoid arthritis / Flow cytometry / Health aspects / Humans / Klinisk medicin / Medical and Health Sciences / Medicin och hälsovetenskap / Medicine / Medicine & Public Health / Orthopedics / Pathogenesis / Patients / Physiological aspects / Population / Rheumatoid arthritis / Rheumatology / Synovial Fluid