Purpose Belimumab, a monoclonal anti-BAFF antibody, has been approved for patients with active systemic lupus erythematosus (SLE) despite standard of care immunosuppressive treatment (ST). However, the interference of belimumab with pathogenetic pathways of SLE is not fully understood. B cell hyperactivity and overexpression of type-I interferons (IFN) have been shown to be key elements in the pathogenesis of SLE. This study shows the effect of belimumab on biomarkers representing B cell hyperactivity and IFN expression in SLE patients.

Methods 20 SLE patients treated with belimumab (BT), 82 SLE patients with ST and 30 matched healthy controls (HC) were recruited. Siglec-1 expression on monocytes representing IFN signature, BCMA expression on different B cell subsets and the frequency of activated naive B cells (aNB) in PBMCs were analysed by FACS. Serum levels of BAFF plus soluble receptors sBCMA and sTACI were determined by ELISA.

Results Compared to ST, BCMA expression was reduced in BT on naive B (p<0.001) and memory B cells (p<0.05) but not on aNB, plasmablasts and plasma cells. In comparison to HC, BCMA expression was similar on all B cell subsets, except on aNB where it was higher in BT (p<0.001). The frequency of aNB among total B cells was reduced in BT compared to ST (p<0.001) and was comparable to HC. Siglec-1 expression on monocytes did not differ significantly between BT and ST; both groups showed a rise compared to HC (each p<0.001). There was no significant difference after belimumab treatment. Furthermore, serum BAFF levels in ST and BT were higher than in HC (each p<0.001), but did not differ significantly between BT and ST. Serum levels of sBCMA (p<0.05) and sTACI (p<0.001) were lower in BT compared to ST and also after belimumab treatment (each p<0.05). BT’s sTACI levels were lower than in HC (p=0.01).

Conclusions This study provides deeper insights into the impact of belimumab on several pathogenetic pathways of SLE activity. Regarding the inhibition of B cell hyperactivity, one key pathogenetic element of SLE, belimumab treatment showed distinct advantages. Furthermore, these results suggested that belimumab treatment did not impair the type-I IFN pathway.