Investigation of the effects of exhausted T cells in childhood systemic lupus erythematosus patients

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement. Although the pathogenesis of the disease is not clear in all aspects, there are important developments with recent studies. Studies to elucidate the pathogenesis of the disease are of great value. In this way, targeted treatment methods can be developed in pediatric patients and the targeted use of drugs suppressing the immune system can reduce disease burden and treatment side effects. In the study, the effects of exhausted T cell, whose place in SLE pathogenesis has not been determined yet, were investigated. The aim of the study is to determine the effects of exhausted T cell co-inhibitor receptors and disease activity by establishing clinical clusters with clinical involvement in SLE in childhood. Forty-nine (49) patients were included in the study. Thirty-five (71.4%) of the patients were girls and 14 (28.6%) were boys. The mean age of the patients in the study was 17.7 ± 2.6 years, and the mean disease duration was 5.7 years (1-17 years, median 5 years). Plasma was separated from the blood sample taken during the evaluation of the patients and the check point inhibitors (IL-2Rα, 4-1BB, CD86, TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, Galectin-9) were studied by cytometric bead sequencing method. Three clinical clusters were formed predominantly with renal involvement, skin involvement and hematological system involvement. There was a difference between these clinical cluster co-inhibitory receptor levels, but it did not reach statistical significance. There was a significant correlation between SLEDAI (SLE Disease Activity Index) disease activity score and IL-2Rα, PD-L1, Galectin-9 among co-inhibitor receptors (p values p = 0.02, p = 0.01, p <0.0001, respectively). When correlation analysis of Galectin-9, a biomarker that reflects IFN signature, with co-inhibitor receptor levels, the same direction as Tim-3 receptor (p <0.0001, r = 0.52) and LAG-3 (p = 0.02, r = 0.42), correlations between CD86 (p <0.0001, r = 0.58) PD-L1 (p = 0.002, r = 0.42), IL-2Rα (p <0.0001, r = 0.69) were detected in the same direction. In the laboratory data evaluated during the visit, it was found that there was an inverse correlation between the count of leukocytes and CD86 (p = 0.02, r = 0.31). There was a reverse correlation between CRP level and PD-1 (p = 0.02, r = 0.34). This study is the first in the literature to investigate the effects of exhausted T cells in childhood SLE patients. Further studies can be conducted on this subject with more patients and patients evaluated during the active period of the disease. Our study will be a guide for other studies on the exhausted T cells, whose place and importance in disease pathogenesis have just been understood.