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B cell alterations during BAFF inhibition with belimumab in SLE

Ramsköld, D., Parodis, I., Lakshmikanth, T. et al.

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.

Citation

Ramsköld, D., Parodis, I., Lakshmikanth, T. et al. "B cell alterations during BAFF inhibition with belimumab in SLE" EBioMedicine (2018): doi: 10.1016/j.ebiom.2018.12.035