Systemic sclerosis (SSc) is a chronic disease characterized by fibrosis, vascular damage, and autoimmunephenomena. The etiology is unknown and the clinical spectrum is highly variable. Our study HYPOTHESIS isthat prognosis in SSc can be predicted by gene expression profiling correlated with clinical, serologic andgenetic/ethnic factors as well as sociodemographic features.
Our SPECIFIC AIMS are as follows: 1) Toperform classification analysis of peripheral blood gene-expression-profiles and skin biopsies from patientswith early limited SSc, early diffuse SSc and matched healthy controls; 2) To compare these profiles in bloodand skin biopsies from patients in the stable chronic phase of diffuse SSc to profiles from early, diffuse SScboth longitudinally (within individual patients) and in cross-sectional fashion (between separate patientgroups); 3) to expand the multi-ethnic (Caucasian, Hispanic, and African-American) GENISOS early-diseaseSSc cohort following subjects longitudinally for disease relevant outcomes: 4) to characterize the cohortaccording to demographics, racial-ethnic background, clinical disease features, autoantibody subsets, HLAand other genetic testing, and socio-behavioral features; 5) To develop a model using the data from aims 1through 4 to identify subsets of patients and predict prognosis; and 6) to provide clinical material from thiscohort to support Project 1 of this CORT. DESIGN and METHODS: SSc patients with <5 years of diseasewill be enrolled and followed at defined intervals using standardized forms. Serial blood samples will beobtained on all and skin biopsies will be done on some participants. Custom printed 50-oligonucleotidemicroarrays representing 19,700 human and 208 Arabidopsis (negative controls) genes will be used andsupervised methods and class comparison will be used to discover differentially regulated genes betweenpredefined classes (e.g., early diffuse SSc vs late diffuse SSc).GEE analysis will be used to examine theassociation between the outcomes (e.g..course of skin disease, pulmonary fibrosis, etc.) and independentvariables (e.g., demographic, HLA, microarray data, etc.) LAY LANGUAGE SUMMARY: This project willstudy patients with the recent onset of scleroderma in order to identify features that distinguish those whowill have mild disease from those who will have a more severe course. This information will help physiciansand patients decide on a treatment plan that is appropriate for their level of disease.
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