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

Author:

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

Abstract

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.

Funder

Göteborgs Läkaresällskap,Sweden

Amlövs Stiftelse

Karolina Widerströms fond

Avtalet om läkarutbildning och forskning

Swedish Science Research Council

The Swedish Rheumatism Association

King Gustav V Stiftelse

IngaBritt och Arne Lundbergs Stiftelse

Lundgrens Stiftelse

Cancerfonden

Barncancerfonden

AFA Försäkring

the Foundation for assistance to disabled people in Skane

University of Gothenburg

Publisher

Springer Science and Business Media LLC

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