Systemic sclerosis

Abstract

Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by vasculopathy and tissue fibrosis of the skin and various internal organs. A series of genetic and epidemiological studies have demonstrated that SSc onset is determined by the accumulation of predisposing factors related to environmental influences, while genetic factors affect the susceptibility to and the severity of this disease. This notion has been confirmed by recent advance in animal models. The initial trigger of SSc is believed to be autoimmune attacks to endothelial cells, which occur in individuals with the genetic susceptibility to autoimmune diseases and/or the cumulative exposure to certain SSc-related environmental influences. Then, endothelial cells are aberrantly activated or damaged, leading to the development of vascular structural changes, such as destructive vasculopathy and proliferative obliterative vasculopathy, and tissue fibrosis. In parallel, inflammatory cells activate SSc fibroblasts and modify the metabolism of extracellular matrix by soluble factors and autoantibodies. Prior to or during these processes, SSc fibroblasts acquire the ability to selectively respond to profibrotic growth factors and cytokines, persistently producing excessive amount of extracellular matrix. SSc fibroblasts also modify immune responses, at least those of CD4 T cells, in the microenvironment through the secretion of immune regulatory molecules. Thus, various types of individually activated cells interact with each other and coordinately drive an SSc-specific disease cascade, leading to the development of unique clinical symptoms. This article provides an overview of the current understanding of the pathogenesis of SSc with the recent advance in the research field of this disease.

Possible association of decreased serum CXCL14 levels with digital ulcers in patients with systemic sclerosis

“…Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by vasculopathy and fibrosis of the skin and various internal organs . Although the etiology of SSc still remains unknown, various clinical and basic studies have provided us lots of clues and insights to better understand its pathogenesis and to further develop its new therapies.…”

“…Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by vasculopathy and fibrosis of the skin and various internal organs. 1 Although the etiology of SSc still remains unknown, various clinical and basic studies have provided us lots of clues and insights to better understand its pathogenesis and to further develop its new therapies. Among various research strategies, clinical studies with sera would be the first, and perhaps the most critical, step to speculate the potential roles of certain target molecules in the three cardinal pathological features of SSc: autoimmunity/inflammation, vasculopathy and tissue fibrosis.…”

Adipose‐derived stromal/stem cells successfully attenuate the fibrosis of scleroderma mouse models

“…However, unfortunately, an effective treatment for SSc has not been established. Emerging evidence indicates that three major abnormalities—autoimmunity, vasculopathy, and fibrosis—are crucial in the pathophysiology of SSc . Immune cells and their components play distinctive roles in SSc development.…”

The association between reproductive factors and systemic sclerosis in Chinese women: A case‐control study and meta‐analysis

“…SSc affects approximately 2 per 10 000 individuals and has significant disability and mortality . Although the etiology of SSc remains unclear, it is generally accepted that a complex interplay between genetic factors, hormone and environmental influences results in the induction of SSc …”