(Taken from the application) Both genetic and nongenetic factors contribute to the predisposition, course and outcome of systemic lupus erythematosus (SLE). We have constituted a cohort of 229 SLE patients from three ethnic groups (Hispanics, African-Americans and Caucasians) at two geographic locations (Alabama and Texas) in order to examine the relative importance of socioeconomic-demographic, behavioral-cultural and immunogenetic features in the clinical manifestations of SLE over time. At disease onset, we found that immunogenetic and ethnic factors primarily accounted for disease activity and specific organ manifestations of SLE (renal, neuropsychiatric and cardiac). At study entry, Hispanics and African-Americans exhibited higher levels of disease activity. Lack of private insurance, abrupt disease onset, anti-Ro antibodies, lack of HLA-DR3 and abnormal illness behaviors, also predicted greater disease activity. Two years into a study, helplessness, poor social support and lack of health insurance predicted persistent disease activity over the study duration. As expected, persistent disease activity as a single factor best predicted disease damage. As more time passes, we are noticing a differential rate of damage accrual in the three ethnic groups, with non-Caucasians having more disease related consequences, although the differences are not yet statistically significant. Despite this, self-perceived functioning was similar in the three groups. Of particular note was that ethnicity per se, independent of genetic factors measured thus far, and socioeconomic-demographic and behavioral-cultural factors, predicted both persistent disease activity and damage, suggesting that other genetic factors are affecting the course of SLE. In this submission, we propose: 1) to continue following the present cohort: 2) to enlarge the present cohort from 229 to 450 patients in order to increase our ability to detect meaningful differences between the three ethnic groups; 3) to examine additional MHC-and non-MHC genes that have also been associated with SLE (TNF, MBP, IL1-RA, Bcl-2); 4) to refine the assessment of those clinical, behavioral-cultural factors found to be important predictors of disease activity, damage and self-perceived functioning thus far; 5) to study the relationship among disease activity, disease damage and self-perceived functioning in these patients as the disease progresses and the factors that predict them. With longer follow-up we expect the impact of the disease will be significantly different among the three ethnic groups and with the addition of new patient recruits we expect to have the power to detect the socioeconomic-demographic, clinical, immunogenetic and behavioral-cultural factors contributing to these differences.
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