Purpose To investigate changes in B cell subsets in relation to renal flares upon initiation of standard therapy (ST) plus belimumab or placebo in patients with systemic lupus erythematosus (SLE).
Methods We analysed data from the BLISS-76, BLISS-SC and BLISS Northeast Asia trials. Circulating CD19+ B cell subsets were characterised through flow-cytometry. We investigated the associations of relative to baseline rapid (through week 8) and early (through week 24) percentage changes in circulating B cell subsets, anti-dsDNA antibodies and complement levels with the occurrence of at least one renal flare during follow-up.
Results Patients who developed renal flares showed a more prominent rapid decrease in CD19+CD20+CD138+ short-lived plasma cells (-50.4% versus -16.7%; P=0.019) and CD19+CD20-CD27bright plasmablasts (-50.0% versus -29.9%; P=0.020) compared with patients who did not flare, followed by a subsequent return to near-baseline values, while patients who did not flare showed gradual yet non-significant decreases in these cell subsets. Remarkably, more prominent rapid reductions in CD19+CD20-CD138+ long-lived plasma cells were associated with a protection against renal flares in belimumab-treated patients (-11.3% versus -29.2%; OR: 1.16; 95% CI: 1.03–1.32; P=0.019), while changes in long-lived plasma cells did not differ between patients who developed renal flares and patients who did not in the subgroup treated with ST alone. Rapid and early changes in anti-dsDNA or complement levels showed no clear association with renal flares.
Conclusions An initial decrease followed by a subsequent return in circulating short-lived plasma cells and plasmablasts upon treatment for active SLE portended renal flares, indicating a need for therapeutic adjustments in selected patients. Rapid decreases in long-lived plasma cells upon belimumab therapy commencement may signify a greater protection against renal flares.
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