This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.OBJECTIVE: To ascertain that the prognosis in systemic sclerosis (scleroderma, SSc) can be predicted by gene expression profiling correlated with clinical, serologic and genetic/ethnic factors as well as sociodemographic features.RESEARCH PLAN: 1. To perform classification analysis of the peripheral blood gene expression profile from patients with early limited SSc, early diffuse SSc and matched healthy controls. 2. To compare gene expression profiles in the periphearl blood from patients with the stable chronic phase of diffuse SSc to profiles from early, progressive, diffuse SSc both longitudinally (within individual patients) in in cross-sectional fashion (between separate patient groups). 3. To expand the multi-ethnic (Caucasian, Hispanic, and African-American) early SSc cohort (GENISOS) following subjects longitudinally for these outcomes: course of skin disease, digital ischemia, gastrointestinal involvement, pulmonary fibrosis, pulmonary hypertension, cardiac involvement, renal crisis, and death. 4. To characterize the cohort according to demographics, racial-ethnic background, clinical disease features, autoantibody subsets, HLA and other genetic testing, and socio-behavioral features. 5. To develop a model using the characteristics of aims 1 athorugh 4 that identifies subsets of patients and predicts prognosis. 6. To provide clinical material from this cohort (skin biopsies, serum, DNA, and peripheral blood cells) to support Project 1 of the CORT.METHODS: Blood will be drawn at the Clinical Research Center at each of the three participating sites. Medical records will be obtained from the appropriate outpatient or inpatient facilities with appropriate authorization from the patient (adhering to HIPAA regulations). Blood for autoantibodies, HLA and other genetic testing will be shipped by overnight carrier to the UT-Houston site. Blood for clinical lab testing is processed and analyzed at the local site. Clinical manifestations and laboratory and other testing report data will be collected on hard copy data collection study forms. Hard copies from UTMB and UTHSC-San Antonio are shipped to the UT-Houston sites, with copies stored at the local site.Subjects who meet the inclusion criteria and lack exclusion criteria will be invited to paticipate in this study. Subjects will be approached in the Rheumatology Clinic offices by the investigators or study coordinators to consider the study. Written informed consent will be obained by the site PI or the study coordinator at each site according to IRB-approved informed consent form and will be followed by their respective local study co-investigator.CLINICAL
SSc patients with early disease (less than five years from disease onset as defined by the date of the first non-Raynaud's phenomenon sign or symptom) have been enrolled into the multi-ethnic CENISOS cohort since 1998 and followed at regular intevals with a defined data collection protocol. A prospective approach provides a level of medical detail and completeness of evaluation that is impossible to obtain by medical record review. This also provides the opportunity to collect serial samples both for immediate and for later studies. One of the greatest values of this prospective cohort is the combination of longitudinal clinical data with simultaneous laboratory collection. An additional value is the multiethnic makeup of the cohort recruting African-American, Hispanic, and Caucasian subjects. As noted above, the African-American ethnicity has been associated with younger age at onset, more diffuse disease and an overall poorer prognosis than their Caucasian counterparts. The reason(s) for this difference is unclear. Although access to care may play a role in prognosis, it does not explain the younger age at onset or greater proportion of diffuse disease. A genetic rationale, in combination with socioeconomic and/or behavioral features may provide the best model for this difference. There are few data regarding SSc disease characteristics in an Hispanic population.
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