COMPLEMENT POLYMORPHISM AND RENAL DISEASE

补体多态性和肾脏疾病

基本信息

批准号：
3152380
负责人：
ROBERT H MCLEAN
金额：
$ 10.94万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-03-01 至 1986-02-28
项目状态：
已结题

项目摘要

The complement (C) system is one of the most important humoral defense systems in man. Activation of either the classical C pathway (C1 through C9) or the alternative C pathway (B, D and C3 through C9) results in the production of biologically active macromolecules and fragments of C components which may be either protective or damaging to the host. Previous investigations of the role of C in disease have primarily focused on changes in serum concentrations and the tissue deposition of C components. We propose for the first time to evaluate the importance of genetically determined polymorphic variants of C components and the relationship to the development of renal disease in children. Despite the remarkable polymorphism of nine of the eleven C components the significance of this polymorphism is not known. Our specific aims are: (1) to determine the frequency of the C4, C3 and B phenotypes in a variety of childhood renal diseases as compared to controls; (2) to correlate C phenotypes with the response to pneumococcal vaccine; (3) to compare biological activities of different C variants (i.e. hemolytic activity, solubilization of immune precipitates) and (4) to correlate C phenotypes with HLA-DR antigens and T-cell subsets. C typing is performed by prolonged electrophoresis in agarose by methods established for C3 and B, and for C4 by recently described methods using neuraminidase treated plasma. Functional C assays employ published methods. Our preliminary evidence shows significant variation from normal for the frequency of certain C phenotypes in the idiopathic nephrotic syndrome, IgA nephropathy, anaphylactoid purpura, recurrent hematuria and juvenile onset lupus erythematosus. Our long term goal is to perform extensive typing of childhood renal disease and to determine whether functional variations can be detected between C phenotypes which may explain a relationship to the development of these diseases. Confirmation of our preliminary findings and the detection of functional differences would present new and potentially important areas of research into the etiology of these common pediatric nephropathies.

补充（C）系统是最重要的体液防御之一人类的系统。激活两种经典C途径（C1通过 C9）或替代C途径（B，D和C3至C9）导致生物活性大分子和C的片段的生产可能对主机保护或损坏的组件。先前对C疾病作用的研究主要集中在疾病中关于血清浓度的变化和C的组织沉积成分。我们首次提出评估的重要性 C成分的遗传确定的多态性变体和与儿童肾脏疾病发展的关系。尽管有十一C组成的九个九个九个的多态性显着性这种多态性尚不清楚。我们的具体目的是：（1）确定各种C4，C3和B表型的频率与对照组相比，儿童期肾脏疾病；（2）关联c 对肺炎球菌疫苗的反应的表型；（3）比较不同C变种的生物学活性（即溶血活性，免疫沉淀物的溶解度）和（4）与C表型相关与HLA-DR抗原和T细胞亚群。 c键入由通过为C3和B建立的方法在琼脂糖中延长电泳，对于C4，最近描述的方法使用已处理的神经氨酸酶等离子体。功能C分析采用已发表的方法。我们的初步有证据表明与正常频率的显着差异特发性肾病综合征的某些C表型，Iga肾病，过敏反刷，复发性血尿和青少年发作狼疮红斑。我们的长期目标是执行大量打字儿童期肾脏疾病并确定功能变化是否可以在C表型之间检测到可以解释与该关系的关系这些疾病的发展。确认我们的初步发现功能差异的检测将呈现新的，并且对这些常见病因的研究的潜在重要领域小儿肾病。