Systemic sclerosis (SSc), or scleroderma is an autoimmune connective tissue disease of unknown etiology. SSc is characterized by excessive production and deposition of collagen in the skin and internal organs. In order to delineate the pathogenic mechanisms which result in debilitating and life-threatening fibrosis, a better understanding of the role played by inherited and/or acquired genetic factors in SSc development is necessary. The goals of this project are (l) to recruit monozygotic and dizygotic twins concordant or discordant for SSc, (2) to detect the presence of SSc-related autoantibodies in the sera of the twin pairs, (3) to determine whether the presence of a specific HLA class II gene in the twins is associated with disease or autoantibody concordance. (4) to identify genes which are differentially expressed in the clinically affected skin of patients with SSc vs. the skin of their identical healthy co-twin, and (5) to characterize the cloned DNAs and the protein products derived from the differentially expressed genes. Confirmation of twin zygosity, autoantibody screening and HLA typing will be done by DNA fingerprinting, immunofluorescence/immunodiffusion/immunoprecipitation and PCR-RFLP analysis, respectively. Identification of differentially expressed gene will be done by DDRT-PCR cloning of PCR products and sequencing of isolated clones. Our study is the first such study involving twins with SSc. It will provide important data on the role (or lack of it) played by inheritance in SSc development as well as allow the detection and identification of new genes whose expression is aberrant in the SSc lesion.
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