NEPHRITOGENIC EPITOPES IN GOODPASTURES SYNDROME

描述（改编自研究者摘要）：人类肾小球肾炎是导致透析或移植的发病率、死亡率和终末期肾病（ESRD）的主要原因。自身免疫性疾病导致大多数形式的肾小球肾炎。多种致病因素参与了肾小球肾炎的最终表现，包括抗体沉积和细胞免疫。许多模型已被广泛研究，以澄清致病机制，但最有可能是诱导的方法不直接相关的man.This调查员开发了一个模型，以检查肺出血肾炎综合征的发病机制，一种疾病与抗体的肾小球基底膜，进行性新月体肾小球肾炎和肺出血。他的研究表明，在用相应的抗原免疫后，会产生各种抗体，而这些抗体中只有一部分会真正引起疾病。翻译后修饰对于致病性抗原的表达可能是关键的。PI假设构成免疫抗原的氨基酸的转录后修饰影响其引起肾炎的能力。具体目的是利用生物化学和分子方法1）鉴定诱导肾小球肾炎的抗原，2）确定是否存在氨基酸的翻译后修饰以及这些修饰可能是什么，3）检查这些修饰的交替对疾病诱导和病程的影响。强有力的证据表明，在这个模型中引起肾小球肾炎的抗原是相同的抗原或位于相同的蛋白质，导致Goodpasture综合征在man.This模型提供了一个机会，为进一步研究自身免疫性肾小球肾炎的致病事件，并允许调查的发病机制，不能在体外完成。从这个模型中获得的信息将提供更好地了解肺出血肾炎综合征和其他类型的自身免疫性肾小球肾炎。此外，从这些调查中获得的知识可能为最终开发Goodpasture综合征的具体治疗干预措施提供基础。

Description (Adapted from Investigator's Abstract): Glomerulonephritis in man is a major cause of morbidity, mortality and end stage renal disease (ESRD) leading to dialysis or transplantation. Autoimmune disease causes most forms of glomerulonephritis. Multiple pathogenic factors are involved in the final expression of glomerulonephritis including the deposition of antibodies and cell mediated immunity. Numerous models have been extensively studied to clarify pathogenic mechanisms, but most likely are induced by methods not directly relevant to man. This investigator has developed a model to examine the pathogenesis of Goodpasture's syndrome, a disease associated with antibody to the glomerular basement membrane, progressive crescentic glomerulonephritis and pulmonary hemorrhage. His studies suggest that a variety of antibodies develop after immunization with the responsible antigen, and that only a subset of these antibodies actually cause disease. Post-translational modification may be critical for expression of the pathogenic antigen. The PI hypothesizes that post-transcriptional modification of the amino acids constituting the immunizing antigen influences its ability to cause nephritis. The specific aims are to utilize biochemical and molecular methods to 1) identify the antigens which induce the glomerulonephritis, 2) determine if post-translational modification of the amino acids are present and what these modifications might be, and 3) examine the effect of alternation of these modifications on disease induction and course. Strong evidence indicates that the antigen which causes glomerulonephritis in this model is the same antigen or is located on the same protein that causes Goodpasture's syndrome in man. This model provides an opportunity for further study of pathogenic events in autoimmune glomerulonephritis and permits investigations of pathogenesis that cannot be accomplished in vitro. Information derived from this model will provide a better understanding of Goodpasture's syndrome and other types of autoimmune glomerulonephritis. Further, the knowledge resultant from these investigations may provide a basis for the eventual development of specific therapeutic interventions for Goodpasture's syndrome.