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。这个 狼疮的异质性和不可预测的病程，以及缺乏可靠的生物标志物来辅助预测 疾病爆发增加了医生治疗这种复杂的系统性疾病患者所面临的挑战。 我们的数据表明T细胞亚群中的去甲基化的CD4+CD28+KIR+CD11a与疾病相关 狼疮患者的活动性。由于T细胞DNA去甲基化在活动期比非活动期更明显 由于去甲基化先于T细胞激活，我们假设 T细胞亚群中的CD4+CD28+KIR+CD11a与狼疮的疾病活动性相关 预测狼疮患者疾病发作的生物标记物。我们将使用横截面和 纵向多中心协作方法。我们建议确定两者之间的关系 红斑狼疮患者T细胞亚群扩增、总遗传风险和SLEDAI评分 并检测T细胞亚群中CD4+CD28+KIR+CD11a作为一种新的预后生物标志物。 一项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.