B cell alterations during BAFF inhibition with belimumab in SLE.

ABSTRACT: BACKGROUND:Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, which exhibits multiple B cell abnormalities including expanded populations of memory B cells and elevated levels of autoantibodies. Belimumab is a monoclonal antibody targeting the B cell cytokine BAFF (a.k.a. BLyS), approved for the treatment of SLE. METHODS:In this prospective cohort study, B cells from peripheral blood of 23 SLE patients initiating belimumab treatment and followed longitudinally for up to three years, were assessed using mass cytometry. FINDINGS:B cells decreased during the study period, with a rapid decrease of both naïve and CD11c+CD21- B cells at the first follow-up visit, followed by a continuous reduction at subsequent follow-ups. In contrast, plasma cells and switched memory B cells remained stable throughout the study. The observed immunological changes correlated with early, but not late, clinical improvements. Moreover, high baseline B cell counts were predictive of failure to attain low disease activity. In summary, our data unveiled both rapid and gradual later therapy-associated alterations of both known and unforeseen B cell phenotypes. INTERPRETATION:Our results suggest that evaluation of B cell counts might prove useful prior to initiation of belimumab treatment and that early treatment evaluation and discontinuation might underestimate delayed clinical improvements resultant of late B cell changes.

SUBMITTER: Ramskold D 

PROVIDER: S-EPMC6412067 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature