Genetics and genomic studies in scleroderma (systemic sclerosis)

Scleroderma or systemic sclerosis is an autoimmune connective tissue disease clinically characterized by fibrosis of the skin and internal organs and obliterative vasculopathy. The complexities of scleroderma are evident from the variability in its clinical manifestations, which probably reflects the diverse mechanisms that underlie the development of disease subtypes. Despite recent advances in the understanding of some of the molecular pathways involved in scleroderma, the etiopathogenesis remains unknown. Although fibrosis and endothelial dysfunction are hallmarks of the disease, autoimmunity is probably the root cause. Autoimmunity and inflammation currently are best exemplified by the multiple but not overlapping patterns of specific autoantibodies in patients who have scleroderma. In fact, each of these autoantibodies tends to mark a distinct clinical subset of disease [1]. The presence of inflammatory infiltrates in the dermis early in the disease and increased circulating levels of cytokines and chemokines in patients who have scleroderma further implicate inflammation in the pathogenesis of scleroderma. It remains unknown how these autoimmune responses lead to certain patterns of organ damage that vary among different clinical subsets of scleroderma.