Purpose of review: Systemic sclerosis (SSc) is a connective tissue disease characterized by early generalized microangiopathy, immune system disturbances and massive deposits of collagen and other matrix substances in the connective tissue. Although rare, SSc presents a major medical challenge, being recognized as the most severe connective tissue disorder in terms of its prognosis. Molecular biology has provided unparalleled insight into the susceptibility genes conferring a predisposition to this disease and has improved our understanding of its complex immune pathogenesis. In this review, we focus on recent large candidate gene studies that have included replication and very recent genome-wide approaches.
Recent findings: Attention has recently focused on both known and new susceptibility genes. Large studies have revealed various striking associations within the immune system, but associations with vascular or fibrotic factors were found to be weaker or were not replicated. The major histocompatibility complex genes are the predominant genetic region of importance for many autoimmune disorders, including SSc. Candidate gene studies and genome-wide studies have also provided evidence that various autoimmune genes implicated in innate immunity, T-cell differentiation and immune signaling play a critical role in this disease.
Summary: The use of powerful molecular tools has shed light on the nature of the susceptibility genes for SSc and the pathophysiology of this disease. Postgenomic studies are now required to clarify the role of these genes. Improvements in diagnostic and prognostic tools are anticipated in the near future, together with the development of more specific immune therapy.