Background Systemic Sclerosis (SSc) is an autoimmune disease characterized by fibrosis and vasculopathy. In patients with active SSc increasing values of the Th17 subset and of pro-fibrotic interleukins such as IL6, IL1 and IL17 were demonstrated, as compared to healthy controls.
Iloprost, a stable prostacyclin analogue, has been shown to down regulate pro-inflammatory cytokines, but its role on T cells modulation is not completely understood
Objectives To evaluate functional T cells subsets in patients with early SSc (eSSc) in basal conditions and after Iloprost treatment
Patients and Methods A total of 7 previously untreated female patients with eSSC (mean age 41.7 years) were enrolled in this study. Two patients were positive for anti-scl70 autoantibodies and five for anti-centromer antibodies, with a mean skin score of 12 (nobody presented digital ulcers) and Medseger score of 5.1 (range 4.8 – 6.7). All patients were treated with i.v. Iloprost (0.3ng/kg for 6 hours in continuous infusion for 5 days). The analysis of T cells subsets, including Th1, TH2, Th17, quiescent CD8 (CD8+/CD38-/HLADR-) and activated CD8 (CD8+/CD38+/HLADR+) was carried out on peripheral blood samples by 8-color flow cytometry. Patients were studied first in basal condition and after 5 days of therapy. Fifteen healthy subjects were studied as controls.
Results Our results shown: a) Low basal absolute values of CD4+T cells in patients with eSSc (mean 776.5/mL, range 424.8/mL-1520.4/mL) vs control group (mean 1048.1/mL, range 642/mL -1683/mL); b) Lower values of percent and absolute CD4+TH17+ cells in the eSSc group, mean 7.66% vs 12.59% (range 4.2% - 12.1% vs 2.7% - 20.3%, p<0.05) and mean 53.92/mL vs 123.1/mL (range 26.34/mL – 87.47/mL vs 45.44/mL-257.8/mL, p<0.05), respectively; c) Reduced baseline quiescent CD8+T cells values and increased activated CD8+T cells after treatment (baseline mean quiescent CD8+ cells: 86.71% and 494.7/mL vs post therapy mean CD8+ cells: 74.54% and 478.3/mL, basal activated CD8+ cells: 1.86% and 13.4/mL vs after treatment activated CD8+ cells: 2.41% and 18/mL), respectively
Conclusions The literature data on T cell regulatory subsets in eSSc are scanty. Our approach included the phenotypic evaluation of CD4+Th17+ cells using CCR6 and CXCR3, so that our measured levels may be higher than those using direct intracellular IL17 evaluation. The low baseline level of CD4+Th17+ cells may be related to the very early phase of the disease, whereas the increase in activated CD8+ cells can be related to the anti-inflammatory and anti-fibrotic effects of Iloprost
Truchetet ME et al. Ann Rheum Dis 2012; 71: 2044-2050. Liu W et al. Prostaglandins Leukot Essent Fatty Acids 2013; 89: 335-344.
Disclosure of Interest None declared