Heterogeneity of peripheral immune cell landscape in systemic lupus erythematosus patients after belimumab treatment.

Abstract

Objectives: The diversity and heterogeneity of circulating immune cells have been extensively investigated in systemic lupus erythematosus (SLE). However, little is known about the influence of belimumab, an anti-BAFF (B cell-activating factor) monoclonal antibody, on the heterogeneity of peripheral immune cell landscape in SLE patients. In this study, we aimed to investigate the altering effect of belimumab on autoimmunity in SLE.

Methods: The single-cell RNA sequence revealed a total of 11 cell clusters by comparing the transcriptome profiles of 24.869 peripheral blood mononuclear cells (PBMCs) from normal controls (NC) and SLE patients with/without belimumab treatment. Flow cytometry was conducted to further confirm the diversity and heterogeneity of peripheral immune cell landscape. The disease-specific T cell, B cell, monocyte (M), and NK cell subpopulations in SLE patients treated with/without belimumab were identified.

Results: Compared to the NC group, SLE patients exhibited a significant upregulation of CD3+T, CD8+T, CD3+PD-1+T, and CD8+PD-1+T cells, while the proportions of CD16+CD56+NK cell, CD14+CD206+ monocyte and CD14+CD163+ monocyte, and the ratio of CD3+CD4+T/CD3+CD8+T were significantly reduced in SLE. After belimumab treatment, the proportions of CD19+B and CD3+PD-1+T cells were significantly decreased in the peripheral blood of SLE patients.

Results: Our study has implicated the substantial heterogeneity and disease-specific immune cell subsets in belimumab-treated and non-belimumab-treated SLE patients. Belimumab treatment may exert therapeutic effects in SLE patients probably by regulating the proliferation, phenotypes and functions of CD19+B cells and CD3+PD-1+T cells, which warrants further investigation in the future particularly regarding their potential roles and molecular mechanisms.