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

BACKGROUND

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.

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.