Immunologic aspects of scleroderma

Many distinct areas of investigation contribute to the understanding of immune abnormalities in systemic sclerosis. Recent immunohistochemical studies question the causal relationship of increased transforming growth factor-beta expression to dermal fibrosis. RNA polymerase I, II, and III have been identified as autoantigens specific for systemic sclerosis. Anti-RNA polymerase antibodies are directed against both unique and shared subunits of the multiprotein complexes. The targeting of several subunits suggests that the entire complexes are processed and presented by antigen-presenting cells. Genetic studies show that both HLA-DR and HLA-DQ genes control the antitopoisomerase response in Japanese patients. The null allele of the complement component C4 and HLA-DQA2 have been identified as two independent disease susceptibility genes.