Genetic/Epigenetic Interactions in Lupus Flares and Remissions

系统性红斑狼疮是一种病因不明的慢性复发性自身免疫性疾病。的 狼疮的异质性和不可预测的过程，以及缺乏可靠的生物标志物来帮助预测 疾病突发增加了治疗患有这种复杂系统性疾病的患者的医生所面临的挑战。 我们的数据表明去甲基化的CD4+CD28+KIR+CD11a hi T细胞亚群与疾病相关， 活动在狼疮患者。由于T细胞DNA去甲基化在活性中比在非活性中更明显， 狼疮患者，因为去甲基化先于T细胞活化，我们假设， CD4+CD28+KIR+CD11a hi T细胞亚群与狼疮疾病活动性相关， 生物标志物来预测狼疮患者的疾病发作。我们将使用一个横截面和 纵向多中心协作方法。我们建议确定 狼疮患者的CD4+CD28+KIR+CD11a hi T细胞亚群扩增、总遗传风险和SLEDAI评分 患者，并测试CD4+CD28+KIR+CD11a hi T细胞亚群大小作为一种新的预后生物标志物， 多中心纵向研究中的疾病进展和缓解。

Systemic lupus erythematosus is a chronic relapsing autoimmune disease of unclear etiology. The heterogeneity and unpredictable course of lupus, and the lack of reliable biomarkers to assist in predicting disease flares add to the challenge faced by physicians treating patients with this complex systemic disease. Our data suggest that a demethylated CD4+CD28+KIR+CD11a hi T cell subset correlates with disease activity in lupus patients. Since T cell DNA demethylation is more pronounced in active compared to inactive lupus patients, and because demethylation precedes T cell activation, we hypothesize that the size of the CD4+CD28+KIR+CD11a hi T cells subset correlates with disease activity in lupus and will be a useful biomarker to predict disease flares in lupus patients. We will test this hypothesis using a cross sectional and a longitudinal multicenter collaborative approach. We propose to determine the relationship between CD4+CD28+KIR+CD11a hi T cell subset expansion, total genetic risk, and the SLEDAI score in lupus patients, and to test the CD4+CD28+KIR+CD11a hi T cell subset size as a novel prognostic biomarker for disease progression and remission in a multicenter longitudinal study.