Belimumab modulates type I interferon signalling in the treatment of systemic lupus erythematosus.

OBJECTIVESTo examine the effects of belimumab on the immune atlas in patients with systemic lupus erythematosus (SLE).

METHODSWe present a single-cell RNA-seq profile of peripheral blood mononuclear cells from six patients with active SLE before and after drug treatment initiation. Three of these patients received belimumab combined with conventional therapy, while three received conventional therapy alone, and served as the control group.

RESULTSWe found that belimumab significantly decreased the number of CD16+ monocytes after 8 weeks of treatment, whereas the opposite was observed in the control group. Compared to conventional therapy, belimumab elicited a significant reduction in IFN-stimulated gene (ISG) activity in monocytes and low-density granulocytes (LDGs). Notably, the expansion of unique subpopulations enriched among ISGs was inhibited in patients treated with belimumab. Moreover, the transcription and expression of BAFF-R and B-cell maturation antigen, two BAFF receptors, was increased in plasmacytoid dendritic cells (pDCs), B cells and plasma cells. However, the expression of BAFF-R was inhibited in monocytes and T cells in patients with SLE.

CONCLUSIONSThese results revealed a novel mechanism of belimumab action, advancing our understanding of the immune atlas in SLE patients before and after belimumab-targeting treatment.