This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A recent multicenter trial of women with systemic lupus erythematosus (SLE) taking estrogens shows that there seems to be two groups of patients, those who develop multiple flares while taking estrogens and those who do not. This protocol is designed to study the effect of estrogens on B-cell function from these two groups of patients by microarray analysis. In addition, genetic polymorphisms in the estrogen receptor and other genes identified by microarray analysis as dysregulated in one or another group will be studied for association with flares/no flares. Patients will be classified as those who undergo flare with estrogens versus those who do not, based on published criteria. Patients will have blood drawn for B-cell studies and genetic studies. B-cell response to estrogen will be determined as protection from B-cell receptor (BCR)-triggered apoptosis and estradiol-mediated reduction in BCR signaling. Also, estradiol-mediated changes in gene expression will be analyzed in the B cells by microarray analysis. Genetic polymorphisms in estrogen receptors and perhaps other genes will be carried out on the samples as well. The pathogenesis of SLE is not well understood, and the contribution of hormones to SLE is even less well understood. This study may identify differences in the way that these women's B cells respond to estrogen and the genes that might be involved.
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