Kerjaschki D
Institut für Klinische Pathologie der Universität Wien.
Verh Dtsch Ges Pathol. 1996;80:139-47.
Heymann nephritis is an extensively studied experimental model of human membranous nephropathy, a currently barely treatable glomerular immune disease. Several basic concepts were discovered by the study of this experiment disease, such as in situ formation of immune deposits, and the roles of the complement system and of oxygen radicals in the development of proteinuria. The major goal of our studies is to develop specific therapies for the experimental and eventually also for the human disease, based on the detailed knowledge of the molecular pathogenic mechanisms. The target of immune deposit forming antibodies was identified as a large membrane glycoprotein with structural similarities with the LDL-receptor. This protein serves as polyspecific receptor, and its intriguing properties in different organs have developed into a separate area of research. Sofar the precise amino acid sequences of several epitopes for the nephritogenic antibodies were identified, thus offering the unique possibility to develop precisely targeted specific therapeutic strategies. Here we link the mechanisms of immune deposit formation with the development of proteinuria.
海曼肾炎是一种经过广泛研究的人类膜性肾病实验模型，而膜性肾病是一种目前几乎无法治疗的肾小球免疫疾病。通过对这种实验性疾病的研究，发现了几个基本概念，如免疫沉积物的原位形成，以及补体系统和氧自由基在蛋白尿形成过程中的作用。我们研究的主要目标是，基于对分子致病机制的详细了解，开发针对实验性疾病的特异性疗法，并最终也用于人类疾病的治疗。形成免疫沉积物的抗体的靶标被确定为一种与低密度脂蛋白受体具有结构相似性的大膜糖蛋白。这种蛋白质作为多特异性受体，其在不同器官中的有趣特性已发展成为一个独立的研究领域。到目前为止，已确定了几种致肾炎抗体的几个表位的精确氨基酸序列，从而为开发精确靶向的特异性治疗策略提供了独特的可能性。在此，我们将免疫沉积物形成机制与蛋白尿的形成联系起来。
