Landscape of immune cells in systematic lupus erythematosus patients with Epstein-Barr virus infection: assessed by single-cell sequencing

Rheumatology (Oxford). 2023 Dec 11:kead673. doi: 10.1093/rheumatology/kead673. Online ahead of print.

Abstract

Objectives: To analyze the immune cell and B cell receptor (BCR) profiles of patients with systematic lupus erythematosus (SLE), with or without Epstein-Barr virus (EBV) infection, and identify the differences between them.

Methods: We included two patients with SLE and positive detection of EBV infections (SLE-EBV+), four with SLE with negative detection of EBV infections (SLE-EBV-), and two healthy controls (HC). Single-cell RNA sequencing (scRNA-seq) was used to investigate the heterogeneity of cell populations by combining the transcriptomic profiles and BCR repertoires.

Results: A total of 83 478 cells were obtained and divided into 31 subtypes. The proportion of CD8+ proliferation T cells were higher in the SLE-EBV+ group than in the SLE-EBV- group. The interferon-alpha/beta pathways were upregulated in most T cells, monocytes, and B-cells in the SLE-EBV+ group, compared with the SLE-EBV- group. Moreover, T cell trajectory indicated CD4+ regulatory T cells (Tregs) may play crucial roles in SLE combined with EBV infection. In the BCR heavy chain, the IGHV3 and IGHV4 gene families were frequently present in all groups. Additionally, Immunoglobin (Ig) M was the largest component of five Ig isotypes, but its proportion was significantly decreased in the SLE-EBV+ group.

Conclusion: This study provides a comprehensive characterization of the immune cell profiles and BCR repertoires of patients with SLE, both with or without concurrent EBV infections, contributing to a better understanding of the mechanism underlying the immune response to EBV infection in patients with SLE.

Keywords: B-cells; T-cells; lymphocytes; systemic lupus erythematosus and autoimmunity; viruses.