Document Type : Original Article

Authors

1 Rheumatology Research Center, Tehran University of Medical Sciences

2 Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

4 Professor of Rheumatology, Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran

5 Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Background: The critical role of IFN signature genes has increasingly been surveyed to determine etiology and pathogenesis of Systemic sclerosis (SSc). IRFs and STATs are mainly considered as transcriptional modulators of IFN-signature genes and type I interferon and play a major role in the regulation of numerous aspects of immune response. The current study was aimed to assess the transcriptional levels of IRF7 and STAT1 mRNAs in PBMCs of scleroderma patients and compare it with healthy subjects.

Methods: In this study, PBMCs were obtained from 50 scleroderma patients and 30 healthy individuals. Subsequently, total RNA extraction from isolated PBMCs and cDNA synthesis was carried out. IRF7 and STAT1 mRNA expressions was conducted by applying quantitative real-time PCR, SYBR Green method, and specific primers for IRF7 and STAT1.

Results: it has been identified that, relative expression of IRF7 was significantly increased in the patients group compared with control group. Moreover, relative expression of IRF7 in Limited SSc (lSSc) and diffuse SSc (dSSc) was significantly increased compared to healthy subjects (P=0.008). The relative expression of STAT1 transcripts in PBMCs of patients group and control group did not represent statistically significant change. The correlation between IRF7 expression and rodnan score of the disease was significant.

Conclusions: IFNs signature genes are involved in the etiopathogenesis of systemic sclerosis. It is suggested that impaired expression of IRF7 transcripts promote the downstream inflammatory cascades in the dermal fibroblasts by the upregulation of Toll-like receptors (TLRs) and by this means, trigger manifestation of SSc-associated symptoms.

Keywords

Main Subjects