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。由于其经常发生的不良反应和缺乏特异性治疗，IgAN代表了严重的健康护理和经济问题。拟议计划项目的总体目标是通过对IgAN或过敏性紫癜（HSP）患者的综合研究来确定这种常见疾病的遗传和分子基础，HSP通常被认为是引起IgAN的疾病过程的全身形式。 我们将招募20个多重家族，其中50名成员患有IgAN或HSP，150名其他家庭成员; 150例散发性IgAN白人患者（无受影响亲属）及其375名家庭成员，50名HSP患者及其125名亲属，50名IgAN非裔美国人患者及其200名家庭成员，50名非IgAN肾小球肾炎患者，200名白人和100名 非裔美国人作为健康对照。该提案基于参与研究者实验室中产生的新发现，涉及IgA分子、免疫复合物和IgA catastrophic相关受体的遗传、生物合成和代谢研究。该计划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肾病的遗传学研究项目2：IgA肾病中IgA 1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：通过参与研究者之间的广泛合作产生的结果可能提供有关IgAN的遗传和分子缺陷特征的信息，明确该病的发病机制，并最终为制定合理的治疗方法提供依据。

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.