Performance of the T cell senescence markers in predicting the active disease of systemic lupus erythematosus

Abstract

Background: Accelerated immunosenescence has been observed in several autoimmune diseases, including systemic lupus erythematosus (SLE). T cell senescence plays an essential role in the destruction of organs in SLE patients. This study aimed to identify the ability of immunosenescence markers to predict SLE disease activity. Methods: Overall, 61 SLE patients and 60 healthy subjects were enrolled in this cross-sectional study. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score assessed disease activity. Senescence surface markers of CD4 and CD8 T lymphocytes were measured by flow cytometry (CD4/CD8 ratio, CD28null, CD57, CD45 isoforms [CD45RA and CD45RO], and KLRG1). Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum cytokines (IFNγ and IL-2) and cytomegalovirus (CMV) serology. Complement and anti-dsDNA levels were also evaluated as the comparator for predicting active disease in SLE. Logistic regression models were used to identify the independent predictive factors for active SLE status. Performance of the senescence markers in predicting active disease in SLE was analyzed by receiver operating characteristic (ROC) curve as the area under curve (AUC). Results: SLE patients with active disease had significantly higher CD8+CD28null, CD8+CD57+, CD8+CD45RA+, CD8+CD45RO+, and CD8+KLRG1+ percentages with lower CD4/CD8 ratio than healthy subjects and SLE patients with inactive disease. The highest AUC and sensitivity were seen in CD8+CD28null (AUC 0.801 [0.662-0.940], sensitivity 91.9%, cut off >6.85%) with comparable results to serum complement and anti-dsDNA in predicting active disease. Multivariate analysis showed that CD4/CD8 ratio, CD8+CD28null, and C3 had significantly increased OR for active SLE. Combination models of CD4/CD8 ratio, CD8+CD28null, and C3 yielded the best results for predicting the active SLE (AUC 0.923 [0.848-0.997], sensitivity 81.2%, specificity 84.0%, LR+ 5.08 and LR- 0.22). Conclusions: Our findings demonstrated that combining immunosenescence markers, including CD4/CD8 ratio and CD8+CD28null with C3 levels could increase the odds of predicting active disease in SLE.