Autoreactive B cells remain active despite clinical disease control in rheumatoid arthritis

• Published in: Journal of autoimmunity Vol. 149; p. 103320
• Main Authors: Neppelenbroek, Sam, Blomberg, Nienke J., Kampstra, Arieke S.B., van der Hem, Joost G.K., Huizinga, Tom W.J., Toes, René E.M., Scherer, Hans U.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2024
• Subjects: Anti-citrullinated protein antibodies; Autoimmunity; Autoreactive B cells; B cell activation; Immunological disease activity; Rheumatoid arthritis; Autoimmunity; Anti-citrullinated protein antibodies; Immunological disease activity; Autoreactive B cells; B cell activation; Rheumatoid arthritis
• ISSN: 0896-8411; 1095-9157; 1095-9157
• DOI: 10.1016/j.jaut.2024.103320

Autoimmune diseases (AIDs) are frequently hallmarked by the presence of autoreactive B cell responses which are involved in disease pathogenesis. However, the dynamics of such responses and their relation to clinical disease activity in humans is poorly understood. Rheumatoid arthritis (RA), a prototypic chronic AID, is hallmarked by B cell responses directed against citrullinated proteins. To determine the relation between the activity of the anti-citrullinated protein antibody (ACPA) B cell response and clinical disease activity in ACPA+ patients with RA. Expression of B cell activation markers by ACPA+, tetanus toxoid (TT)+ and ACPA− memory B cells (MBCs) from peripheral blood of ACPA+ RA patients receiving different treatments was analyzed by flow cytometry. Results were correlated to clinical disease activity. Compared to TT+ and ACPA− MBCs, ACPA+ MBCs displayed a highly activated phenotype as evidenced by increased expression of Ki-67, CD86, CD80, CD19 and CD20 and reduced expression of CD32. The activated phenotype of ACPA+ MBCs did not associate with clinical disease activity in a cross-sectional analysis of RA patients treated with various therapeutic agents. Also, in a longitudinal analysis of patients treated with Janus kinase (JAK) inhibitors, ACPA+ MBCs retained their activated phenotype despite effective control of inflammation and clinical disease. ACPA+ MBCs remain active despite clinical disease control in patients with RA across a range of interventions. This persistent activity indicates the absence of immunological remission and might explain why ACPA+ patients rarely reach sustained drug-free remission and frequently flare upon drug tapering. •Autoreactive B cells in rheumatoid arthritis are active despite clinical control of disease.•The activated phenotype of autoreactive B cells does not associate with clinical disease activity in patients treated with csDMARDs or TNF-α inhibitors.•Janus kinase inhibitors did also not revert the activation of autoreactive B cells towards a resting state.