TUBULOINTESTITIAL NEPHRITIS/BASEMENT MEMBRANE ANTIGENS

某些类型肾小管间质性肾炎的发病机制 涉及针对肾小管基底膜（TBM）的抗体 或密切相关的间质抗原。 为了彻底 阐明本病的免疫发病机制， 以确定所涉及的抗原的特性。 到目前为止， 很少有人发表有关的特点， 这些抗原。 这项研究的目的是从生物化学的角度 表征被抗TBM血清识别的抗原 肾小管间质性肾炎（TIN）。 抗原是 研究已获得了一个未降解的形式，通过提取 变性溶剂中的TBM，并通过离子交换、凝胶 过滤和反相HPLC。 抗原将是 其特征在于其氨基酸和碳水化合物组成， 其氨基末端序列和精确分子量。 的 抗原与细胞外基质的其他组分的结合 矩阵将被检查，以阐明其功能 正常肾脏中的相互作用。 结构和功能 结构域将在来自 通过测试它们执行抗原结合功能的能力， 完整分子及其在大鼠中诱导TIN的能力 模型 使用的方法包括色谱法 分离，化学分析，电泳分析， 免疫化学测定、蛋白质结合测定和蛋白质 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。 这也将有助于我们 了解TIN的发病机制和结构， 基底膜和细胞外基质的功能 件. 将制备的抗原及其片段 可能有助于诊断各种形式的 肾炎，并用于治疗的效果。 新型 可以开发出包括特异性去除有毒物质的治疗方法， 自身抗体和/或破坏性淋巴细胞从 流通

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.