Familial IgA Nephropathy: Genetic and Metabolic Studies

IgA肾病(IgAN)是世界上最常见的原发性肾小球肾炎。由于IgAN的不良病程和缺乏特异性治疗，它代表了一个严重的卫生保健和经济问题。拟议项目的总体目标是通过对IgAN或过敏性紫癜（HSP）患者的综合研究确定这种常见疾病的遗传和分子基础，HSP通常被认为是导致IgAN的疾病过程的系统性形式。我们将招募20个多重家庭，其中有50名患有IgAN或HSP的成员和150名其他家庭成员；150例散发性IgAN白种人患者（无受影响亲属）及其375名家属，50例HSP患者及其125名亲属，50例非裔美国人IgAN患者及其200名家属，50例非IgAN肾小球肾炎患者，200例白种人和100例非裔美国人作为健康对照。本提案基于参与研究者在实验室中产生的关于IgA分子、免疫复合物和参与IgA分解代谢的相关受体的遗传、生物合成和代谢研究的新发现。项目包括三个组成部分的研究项目和两个核心设施：项目1:IgA肾病的遗传研究项目2:IgA肾病中IgA1分子的生物合成和糖基化项目3:IgA肾病中的免疫复合物和系膜细胞核心A：临床资源和生物统计学核心B：通过参与研究人员之间的广泛合作产生的结果可能提供有关IgAN遗传和分子缺陷特征的信息，确定该疾病的发病机制，并最终为制定合理的治疗方法提供基础。

IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world. Because of its frequently unfavorable cou7rse and lack of specific therapy, IgAN represents a serious healthy care and economic problem. The overall objective of the proposed Program Project is to determine the genetic and molecular basis of this common disease through integrated studies of patients with IgAN or Henoch-Schonlein purpura (HSP), commonly considered the systemic form of the disease process causing IgAN. We will enroll 20 multiplex families with 50 member5s afflicted with IgAN or HSP and 150 other family members; 150 Caucasian patients with sporadic IgAN (no affected relatives) and 375 of their family members, 50 patients with HSP and 125 of their relatives, 50 African-American patients with IgAN and 200 family members, 50 patients with non-IgAN glomerulonephritis, and 200 Caucasians and 100 African-Americans as health controls. This proposal is based on novel findings generated in the laboratories of the participating investigators, with respect to genetic, biosynthetic, and metabolic studies of IgA molecules, immune complexes, and relevant receptors involved in IgA catabolism. The Program Project consists of three component research project and two core facilities: Project 1: Genetic Studies of IgA Nephropathy Project 2: Biosynthesis and Glycosylation of IgA1 Molecules in IgA Nephropathy Project 3: Immune Complexes and Mesangial Cells in IgA Nephropathy Core A: Clinical Resources and Biostatistics Core B: Administrative The results generated through extensive collaboration among the participating investigators are likely to provide information concerning the genetic and molecular defects characteristic of IgAN, identify mechanisms of the pathogenesis of this disease, and ultimately provide a basis to develop rational therapeutic approaches.