CyTOF analysis of immune characteristics in cSLE: belimumab treatment and refractory cases

TL;DR

This study uses CyTOF to analyze immune changes in children with lupus before and after belimumab treatment, identifying key B cell and T cell patterns linked to treatment response and disease severity.

Contribution

The study provides novel insights into immune cell dynamics in pediatric lupus patients treated with belimumab, highlighting CD38 and CD73 as potential biomarkers.

Findings

Belimumab treatment reduced transitional and naïve B cells and age-associated B cells in cSLE patients.

Plasma cells and plasmablasts persisted in refractory cases, suggesting a role in disease resistance.

CD38 expression on B cells correlated with disease activity, while CD73 increased during recovery.

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs. Some patients still develop severe refractory SLE despite conventional treatments. Belimumab, a biologic targeting B lymphocyte stimulator (BLyS), shows therapeutic promise in SLE, but its effects on pediatric patients remain unclear.

This study used CyTOF to analyze immunophenotypic changes before and after belimumab treatment and investigate immune features in refractory SLE.

Results showed that belimumab treatment primarily reduced transitional and naïve B cells, and also decreased age-associated B cells (ABCs), a subset implicated in autoimmunity or chronic inflammation. Plasma cells and plasmablasts persisted in refractory cases. CD38 expression on B cells was elevated in severe disease and correlated with disease activity, while CD73 expression increased during recovery and inversely correlated with activity.

These findings indicate that combining belimumab with conventional therapy induces significant immune modulation, particularly within B cells. Persistent plasma cells and plasmablasts may contribute to disease refractoriness. CD38 and the CD73-mediated adenosine pathway may provide insights for future research strategies in SLE.

Using high-dimensional CyTOF, this study characterized immune cell dynamics in childhood-onset SLE (cSLE) during belimumab treatment. Belimumab primarily led to a reduction in transitional and naïve B cells. Plasma cells and plasmablasts persisted in refractory patients, highlighting CD38 as a feature of interest. CD73 upregulation on B cells correlated with reduced disease activity, suggesting a potential role for the CD73-mediated adenosine pathway in immune modulation. Childhood-onset systemic lupus erythematosus, Biologics, BlyS, CD38, CD73.CyTOF analysis diagram showing immune characteristics in cSLE with Belimumab treatment. Left panel illustrates treatment paths: conventional treatment leads to SLE-SR, Belimumab leads to SLE-T1 and SLE-T4. Mass cytometry analyzes PBMCs. Right panel details changes: transitional and naive B cells decrease in SLE-T4, switched memory B cells increase in SLE-T4, plasma cells increase in SLE-SR. T cell changes show naive CD4+ T cells decrease, Th1 cells increase in SLE-SR. Specific markers CD38 and CD73 have positive and negative correlations with SLEDAI, respectively.

Using high-dimensional CyTOF, this study characterized immune cell dynamics in childhood-onset SLE (cSLE) during belimumab treatment. Belimumab primarily led to a reduction in transitional and naïve B cells. Plasma cells and plasmablasts persisted in refractory patients, highlighting CD38 as a feature of interest. CD73 upregulation on B cells correlated with reduced disease activity, suggesting a potential role for the CD73-mediated adenosine pathway in immune modulation. Childhood-onset systemic lupus erythematosus, Biologics, BlyS, CD38, CD73.

Figures