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FRI0491 Possible Role of Iloprost in Vivo on T-Lymphocyte Regulation Pathway in Early Systemic Sclerosis (ESSC)
  1. P. Faggioli1,
  2. A. Gatti2,
  3. A. Mazzone1,
  4. A. Sciascera1,
  5. A.G. Gilardi1,
  6. B. Brando2
  1. 1Internal Medecine Legnano
  2. 2laboratory and Transfusion Center, AO Ospedale Civile Legnano, Legnano, Italy

Abstract

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

References

  1. 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

DOI 10.1136/annrheumdis-2014-eular.5774

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