IMMUNOPATHOGENETIC MECHANISMS IN RENAL DISEASE

肾脏疾病的免疫致病机制

• 批准号: 3226128
• 负责人: ROBERT T MCCLUSKEY
• 金额: $ 17.34万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-05-01 至 1990-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3226128
• 关键词: antiidiotype antibody; autoantibody; basement membrane; disease /disorder model; electron microscopy; glomerulonephritis; histochemistry /cytochemistry; human tissue; immune complex diseases; immunization; immunoelectron microscopy; immunofluorescence technique; immunoglobulin G; immunopathology diagnosis; immunotherapy; kidney disorder diagnosis; laboratory mouse; laboratory rabbit; laboratory rat; monoclonal antibody; nephritis; radioimmunoassay; radiotracer; renal glomerulus; scanning electron microscopy; serology /serodiagnosis; surface antigens; tissue /cell culture

The main objective of the project is to investigate the pathogenesis of membranous glomerulonephritis, which is a fairly common form of chronic renal disease in man. Although the disease is assumed to result from deposition of immune complexes in glomeruli, the identity of tha antigen(s) and the specificities of the antibodies in the deposits are unknown. The hypothesis to be tested is that the glomerular deposits result from the interaction of autoantibodiees with antigens on the surface of glomerular epithelial cells. This hypothesis is based on findings in Heymann nephritis, an experimental model in rats that closely resembles the human disease. Autoantibodies reactive with glomerular epithelial cells will be sought in patients with membranous nephritis, by the use of approaches developed in studies on Heymann nephritis, in particular by the use of cultured glomerular epithelial cells as substrates. In addition, monoclonal antibodies will be prepared by immunization of mice with antigen preparations obtained from normal renal tissue or from specimens of membranous nephritis, with the aim of obtaining antibodies that identify nephritogenic antigens. Other studies will be concerned with heymann nephritis. The nature and possible interaction of two identified nephritogenic antigens (gp 330 and a 95 kd antigen) will be investigated, in particular with respect to the mechanism of formation of glomerular deposits. In addition, the degree of idiotypic heterogeneity of the autoantibodies will be studied, and experiments will be performed to determine if antiidiotypic antibodies can modify Heymann nephritis.

该项目的主要目的是研究 膜性肾小球肾炎，这是一种相当常见的慢性肾小球肾炎， 肾脏疾病的人。虽然这种疾病被认为是由于 免疫复合物在肾小球中的沉积，THA抗原的特性 并且沉积物中抗体的特异性是未知的。 的 有待检验的假设是，肾小球沉积物是由 自身抗体与肾小球表面抗原的相互作用 上皮细胞 这一假设是基于海曼的发现 肾炎，一种与人类非常相似的大鼠实验模型， 疾病 与肾小球上皮细胞反应的自身抗体将是 寻求在膜性肾炎患者，通过使用的方法， 在海曼肾炎的研究中，特别是通过使用 培养的肾小球上皮细胞作为底物。 此外，本发明还提供了一种方法， 通过用抗原免疫小鼠制备单克隆抗体 从正常肾组织或从 膜性肾炎，目的是获得抗体， 致肾炎抗原 其他研究将关注海曼肾炎。 的性质和 两种已鉴定的致肾炎抗原（gp 330和a 95 kd抗原），特别是关于 肾小球沉积物的形成机制。 此外， 将研究自身抗体的独特型异质性， 将进行实验以确定抗独特型抗体是否可以 改良Heymann肾炎。