The factors contributing to the treatment efficacy of belimumab in patients with systemic lupus erythematosus (SLE) in the maintenance phase are unknown. Here, we collected blood samples from patients with SLE (n=44) treated with belimumab before and three and six months after treatment. RNA-Seq of whole blood was performed, and gene expression was quantified. Immune cell type enrichment analysis estimated immune cell subtype proportions and gene expression in each subtype. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) <
4 at six months was set as the primary efficacy criterion. Non-responders exhibited upregulated B cell proliferation signals before treatment, associated with an increased number of memory B cells. A higher proportion of memory B cells before treatment predicted poor response (