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

• Published in: Arthritis research & therapy 2024-01, Vol.26 (1), p.23-23, Article 23
• Main Authors: Thorarinsdottir, Katrin, McGrath, Sarah, Forslind, Kristina, Agelii, Monica Leu, Ekwall, Anna-Karin Hultgård, Jacobsson, Lennart T H, Rudin, Anna, Mårtensson, Inga-Lill, Gjertsson, Inger
• Format: Article
• Language: English
• Subjects: Arthritis, Rheumatoid - pathology; Articular cartilage; Autoantibodies; B cells; B-Lymphocyte Subsets; B-Lymphocytes; Cartilage; Cartilage - pathology; Cartilage destruction; CD21 DN B cells; 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; Pathogenesis; Patients; Physiological aspects; Population; Reumatologi och inflammation; Rheumatoid arthritis; Rheumatology; Rheumatology and Autoimmunity; Synovial Fluid
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-024-03264-2

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 B cells, have been linked to autoimmune diseases, including RA. In this study, we characterized the CD21 and CD21 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. 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. 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 CD27 IgD subset. The only B cell subset found to associate with clinical factors was the CD21 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 DN B cells were expanded and these cells expressed receptor activator of the nuclear factor κB ligand (RANKL). Cartilage destruction in eRA patients was associated with an expanded proportion of CD21 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 DN in RA pathogenesis.