Genetics and pathophysiology of systemic sclerosis

Systemic sclerosis (SSc) is a connective tissue disease characterized by early generalized microangiopathy, immunological disorders, and massive overproduction and accumulation of collagen and other matrix components in connective tissue. Although rare, SSc may be considered as is the most severe connective tissue disorder and a major medical challenge. Molecular biology has led to notable progress into genetic predisposing factors and the complex pathogenesis of SSc. Large scale studies have revealed robust genetic associations with several factors involved in autoimmunity, while associations with vascular and fibrotic factors are weaker or have not been independently replicated. The major histocompatibility complex genes are the most important genomic region in many autoimmune disorders, including SSc. Candidate-gene and genome-wide studies point to a key role of genes encoding proteins involved in innate and adaptive immunity. Interactions between genes and environmental factors need to be further investigated. Improvements in diagnostic and prognostic tools are anticipated in the near future, together with more specific immune therapy for these patients, for whom specific treatment is not currently available.