Association between senescence of T cells and disease activity in patients with systemic lupus erythematosus

Handono Kalim; Cesarius Singgih Wahono; Bunga Petriana Oktarini Permana; Mirza Zaka Pratama; Kusworini Handono

doi:10.5114/reum.2021.110318

Association between senescence of T cells and disease activity in patients with systemic lupus erythematosus

Reumatologia. 2021;59(5):292-301. doi: 10.5114/reum.2021.110318. Epub 2021 Oct 25.

Authors

Handono Kalim¹, Cesarius Singgih Wahono¹, Bunga Petriana Oktarini Permana¹, Mirza Zaka Pratama¹, Kusworini Handono²

Affiliations

¹ Rheumatology and Immunology Division, Department of Internal Medicine, Faculty of Medicine, Brawijaya University, Saiful Anwar General Hospital, Malang, Indonesia.
² Department of Clinical Pathology, Faculty of Medicine, Brawijaya University, Saiful Anwar General Hospital, Malang, Indonesia.

Abstract

Objectives: Systemic lupus erythematosus (SLE) patients are predisposed to chronic immune activation, leading to accelerated immunosenescence. The aging of the immune system causes the T cells to express several senescence markers such as CD57 and KLRG1, which produce pro-inflammatory cytokine interferon γ (IFN-γ). Immunosenescence was associated with high morbidity and mortality in other diseases. This research was conducted to prove the association between senescent T cells and SLE disease activity.

Material and methods: This research was an observational cross-sectional study on 53 women aged 16-45 years diagnosed with SLE based on SLICC 2012 criteria. All subjects were recorded for demographic and clinical data, and their SLE disease activity index (SLEDAI) score was measured to evaluate disease activity. Active disease was defined as SLEDAI score ≥ 3. The CD57 antigen and KLRG1 expression on CD4+ and CD8+ T cells were calculated from peripheral blood mononuclear cells (PBMC) by flow cytometry. Interferon γ was measured from serum using ELISA. The comparison was done using the Mann-Whitney U test, and correlation was tested using the Spearman test. Associations between variables were calculated using linear regression models.

Results: Systemic lupus erythematosus patients with active disease had markedly higher CD4+KLRG1+ (3.1 [1.3-5.5]% vs. 0.3 [0.1-0.5]%), CD8+CD57+ (11.6 ±7.1% vs. 2.4 ±2.0%, p = 0.000), and CD8+KLRG1+ T cell percentages (13.7 ±7.5% vs. 0.3 ±0.1%, p = 0.000), and IFN- γ levels (208.9 [148.3-233.8] vs. 146.7 [130.2-210.8] pg/ml, p = 0.048), compared to the inactive patients. Positive correlation and association was found between the CD8+CD57+ and CD8+KLRG1+ percentages with the SLEDAI score (p = 0.007 and p = 0.007, for the linear regression analysis, respectively).

Conclusions: Systemic lupus erythematosus patients showed significantly higher senescence T cell markers compared to controls, and the increase of T cell senescence, especially in the CD8 compartment, has some association with increased disease activity in patients with SLE.

Keywords: T cell senescence; immunosenescence; systemic lupus erythematosus; systemic lupus erythematosus disease activity index.