The reduced frequency of CD39+CD73+ B cell subsets in SLE patients is correlated with disease activity

Abstract

Background

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by immune mechanisms dysregulation, leading to the production of diverse autoantibodies. However, the immune pathways underlying B-cell function and phenotypic abnormalities related to SLE pathogenesis remain incompletely understood.

Objective

To explore new markers of SLE activity and potential targets for SLE immunotherapy.

Methods

Collect peripheral blood mononuclear cells (PBMCs) from SLE patients and healthy controls (HC). Use flow cytometry to detect CD39 and CD73 expression on B cell subsets and enzyme-linked immunosorbent assay (ELISA) to measure adenosine (ADO) concentrations in SLE patients’ serum. Compare CD39⁺CD73⁺ B cell subsets frequency and ADO concentrations in SLE patients and HC group. Additionally, analyze the correlation between CD39⁺CD73⁺ B cell subsets frequency and clinical laboratory parameters.

Results

CD39 and CD73 are simultaneously highly expressed on CD19⁺ B cell subsets, with significantly lower frequency of CD39⁺CD73⁺ B cell subsets in SLE patients compared to HC group. This frequency negatively correlates with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), C-reactive protein (CRP), and anti-double-stranded DNA (anti-dsDNA) antibodies, while positively correlating with IgM and prothrombin time (PT). Additionally, the frequency of CD39⁺CD73⁺ B cell subsets is significantly negatively correlated with IL-6 and IFN-α. In vitro cell experiments demonstrate that adenosine significantly inhibits R848-induced inflammatory cytokine production in a dose-dependent manner.

Conclusion

The frequency of CD39⁺CD73⁺ B cell subsets of SLE patients is decreased, correlating with clinical laboratory parameters and disease activity. Simultaneously, ADO concentration in the patients’ serum is reduced. The CD39⁺CD73⁺ B cell/ADO pathway may represent a novel immunotherapy strategy for SLE.