Disturbance in Serum Levels of IL-17 and TGF-β1 and in Gene Expression of ROR-γt and FOX-P3 Is Associated with Pathogenicity of Systematic Lupus Erythematosus.

Abstract

To investigate the disturbance in serum levels of interleukin-17 (IL-17) and transforming growth factor-beta1 (TGF-β1) and gene expression of retinoic acid-related orphan receptor-gamma t (ROR-γt) and forkhead box-P3 (FOX-P3) in patients with systemic lupus erythematosus (SLE) and to study their association with disease pathogenicity and activity. Newly diagnosed active patients with SLE (n=88) and healthy volunteers (n=70) were included. Serum IL-17 and TGF-β1 were measured using enzyme-linked immunosorbent assay. Gene-expression profiles of ROR-γt and FOX-P3 were screened using real-time polymerase chain reaction. The IL-17/TGF-β1 and ROR-γt/FOX-P3 levels were also calculated. The mean age of the patients was 30.96±8.25 years; they were 82 women and 6 men. Of the patients, 11.4% manifested mild disease while 88.6% had severe disease. The serum level of TGF-β1 was significantly lower (70.2±34.9 vs. 200.23±124.77 pg/ml), while both IL-17 (614.7±317.5 vs. 279.76±110.65 pg/ml) and IL-17/TGF-β1 (18.5±30.1 vs. 1.66±0.9) levels were significantly higher, in patients than in controls (p<0.0001). The gene-expression level of FOX-P3 (0.6±0.8 vs. 13.68±39.35) was reported to be lower, while ROR-γt (3.9±3.5 vs. 1.99±2.09) and ROR-γt/FOX-P3 (18.6±21.1 vs. 7.63±17.19) levels were significantly higher, in patients than in controls (p<0.0001). Disturbance in serum levels of IL-17 and TGF-β1 in T helper-17 and T-regulatory cells proliferation was highlighted through an imbalance in the gene expression of FOX-P3 and ROR-γt, as both are signature genes for the two cell types, respectively. These findings underscore the critical role of IL-17 and TGF-β1 in SLE development, rendering them potential targets for developing novel immunotherapeutic strategies.