The role and clinical significance of programmed cell death- ligand 1 expressed on CD19+B-cells and subsets in systemic lupus erythematosus

Abstract

Background: Programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1)-targeted therapies have enhanced T-cell response and demonstrated efficacy in the treatment of multiple cancers. However, the role and clinical significance of PD-L1 expression on CD19⁺ B-cells and their subsets, with particular reference to systemic lupus erythematosus (SLE), have not yet been studied in detail.

Objective: The present study aimed to investigate PD-L1 expression on CD19+ B-cells and their subsets, in addition to exploring its possible role in Tfh-cell activation and B-cell differentiation in SLE.

Methods: Frequencies of CD19⁺ B-cells, their subsets, PD-L1 and Tfh cells in the peripheral blood of SLE patients and healthy controls (HCs) were determined using cytometry. The clinical data of SLE patients were recorded in detail, and the correlation between their laboratory parameters, clinical parameters and disease activity indices was statistically analyzed. CD19⁺PD-L1⁺B-cells and CD19⁺PD-L1^- B-cells were sorted and cultured with a stimulant, following which the supernatants were collected for immunoglobulin G and anti-double stranded DNA detection via enzyme-linked immunosorbent assay.

Results: In SLE patients, CD19⁺B-cells and partial subgroups were enriched in peripheral blood. Also, the observed increase in the frequency of CD19⁺PD-L1⁺B-cells was significantly associated with a higher disease activity index. An in vitro culture test demonstrated that the amounts of anti-dsDNA and immunoglobulin G secreted by the CD19⁺PD-L1⁺B-cells of SLE patients and HCs were vastly different. In addition, a strong correlation existed between the frequencies of CD19⁺PD-L1⁺B-cells and defined Tfh cells of SLE patients.

Conclusion: This study demonstrated that the expression of CD19⁺PD-L1⁺B-cells in the peripheral blood of SLE patients was abnormal, and that disease-related laboratory parameters and clinical indicators were correlated. CD19⁺PD-L1⁺B-cells were enriched and played a critical role in activating the pathogenic T-cell and B-cell responses in patients with SLE.

Keywords: CD19(+) B-cell; PD-L1; Systemic lupus erythematosus; Tfh.