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.

Keywords: Adenosine; B cell; CD39; CD73; SLE; SLEDAI.