Imbalance between Th17 and regulatory T cells in patients with systemic lupus erythematosus combined EBV/CMV viraemia

Clin Exp Rheumatol. 2020 Sep-Oct;38(5):864-873. Epub 2019 Nov 20.

Abstract

Objectives: Infection is one of the leading causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Excessive use of glucocorticoids, disease-modifying anti-rheumatic drugs (DMARDs) and immune disturbances associated with lupus itself lead to reduced immune function with consequent increases in opportunistic infections, such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV). A recent study showed that an imbalance between T helper 17 (Th17) cells and regulatory T (Treg) cells is a major cause of autoimmune disease. However, the relationship between Th17/Treg imbalance and SLE combined with EBV and/or CMV is unknown. Here, we investigated lymphocyte subsets, especially CD4+ T cells, in patients with SLE combined with EBV/CMV viraemia.

Methods: The clinical records of 36 SLE patients with EBV and/or CMV viraemia (SLE infection group), hospitalised at the Second Hospital of Shanxi Medical University, were analysed. As controls, we selected 20 healthy subjects (healthy control group), 30 SLE patients without infection (SLE non-infection group), and 20 patients with other non-SLE connective tissue diseases with EBV/CMV viraemia (non-SLE infection group), the controls were age-matched with the SLE infection group. The absolute numbers of lymphocytes and CD4+ T cells in peripheral blood were examined by flow cytometry.

Results: There were significant decreases in Th17 and Treg levels in the SLE infection group compared to the SLE non-infection group and non-SLE infection group. Similarly, the absolute numbers of Th17 (p=0.003) and Treg (p<0.001) cells in the SLE infection group were markedly decreased compared to the healthy controls, although the difference in Th17/Treg cell ratio was not significant. The absolute number of Treg cells (p=0.001) was decreased in the SLE non-infection group compared to the healthy controls, leading to a higher Th17/Treg cell ratio in the former group (p=0.018). There was no significant difference in the absolute number of Th17 cells between the SLE non-infection group and healthy controls.

Conclusions: The monitoring of lymphocytes and CD4+ T cell subsets, especially Th17 and Treg cells, may be helpful for identifying EBV/CMV infection in SLE patients. The results presented here suggest that, in addition to Treg, Th17 may also be crucial in the Th17/Treg imbalance seen in patients with SLE combined with EBV and/or CMV viraemia. A decrease in Th17 cells may be an important feature of EBV and/or CMV infection in SLE. Appropriate immunomodulatory therapy for CD4+ T cell subsets based on antiviral therapy may be beneficial for SLE patients with EBV and/or CMV viraemia.

MeSH terms

  • Cytomegalovirus Infections*
  • Herpesvirus 4, Human
  • Humans
  • Lupus Erythematosus, Systemic*
  • T-Lymphocytes, Regulatory
  • Th17 Cells
  • Viremia