TUBULOINTESTITIAL NEPHRITIS/BASEMENT MEMBRANE ANTIGENS

几种形式的肾小管间质肾炎的发病机制 涉及针对小管基底膜的抗体(TBM) 或紧密相关的间质抗原。为了完全 阐明该病的免疫发病机制十分必要。 以确定所涉及的抗原的性质。到目前为止， 关于这一特征的文献很少。 这些抗原。这项研究的目标是在生物化学上 鉴定可被抗TBM血清识别的抗原 人肾小管间质性肾炎(TIN)。未来的抗原是 所研究的是通过提取的非降解形式 在变性溶剂中，并通过离子交换、凝胶纯化 过滤和反相高效液相色谱。抗原将会是 以其氨基酸和碳水化合物组成为特征， 其氨基末端序列和准确的相对分子质量。这个 抗原与细胞外其他成分的结合 将对矩阵进行检查，以阐明其功能 正常肾脏中的相互作用。结构和功能 域将在派生自 通过测试它们执行结合功能的能力来识别抗原 完整的分子及其在大鼠体内诱导TIN的能力 模特。 将使用的方法学包括色层分析 分离，化学分析，电泳法， 免疫化学分析、蛋白质结合分析和蛋白质 用酶和化学试剂消化。 这项研究将有助于申请人的长期目标 了解细胞外基质的结构和功能 健康和疾病的组成部分。它还将有助于我们的 对TIN的发病机制及其结构和功能的认识 基底膜和细胞外基质的功能 组件。将制备的抗原及其片段 可能有助于诊断各种形式的脑血管意外 肾炎，并用于后续治疗的效果。新的种类 可以开发出专门清除有毒物质的治疗方法 自身抗体和/或破坏性淋巴细胞来自 发行量。

The pathogenesis of some forms of tubulointerstitial nephritis involves antibodies toward the tubular basement membrane (TBM) or closely associated interstitial antigens. In order to completely elucidate the immunopathogenesis of this disease it is necessary to determine the properties of the antigens involved. To date, very little has been published regarding the characteristics of these antigens. The goal of this research is to biochemically characterize an antigen that is recognized by the anti-TBM sera in human tubulointerstitial nephritis (TIN). The antigen to be studied has been obtained in an undegraded form by extraction of TBM in denaturing solvents, and purified by ion-exchange, gel filtration and reverse phase HPLC. The antigen will be characterized for its amino acid and carbohydrate composition, its amino terminal sequence and exact molecular weight. The binding of the antigen to other components of the extracellular matrix will be examined in order to elucidate its functional interactions in the normal kidney. Structural and functional domains will be identified within fragments derived from the antigen by testing their ability to perform the binding functions of the intact molecule, and their ability to induce TIN in a rat model. The methodology to be used includes chromatographic separations, chemical analysis, electrophoresis analysis, immunochemical assays, protein binding assays and protein digestion by enzymes and chemical reagents. The study will contribute to the applicant's long-term objective of understanding the structure and function of extracellular matrix components in health and disease. It will also contribute to our understanding of the pathogenesis of TIN and of the structure and function of basement membranes and extracellular matrix components. The antigen and its fragments that will be prepared could be useful in establishing diagnosis of various forms of nephritis, and for following the effects of therapy. New kinds of therapy could be developed involving specific removal of toxic autoantibodies and/or destructive lymphocytes from the circulation.