Ying W Z, Sanders P W
Department of Medicine, Nephrology Research and Training Center, Comprehensive Cancer Center, and Cell Adhesion and Matrix Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Am J Pathol. 2001 May;158(5):1859-66. doi: 10.1016/S0002-9440(10)64142-9.
Cast nephropathy, or myeloma kidney, is a potentially reversible cause of chronic renal failure. In this condition, filtered light chains bind to a common site on Tamm-Horsfall protein (THP), which is produced by cells of the thick ascending limb of the loop of HENLE: Subsequent aggregation of these proteins produces casts that obstruct tubule fluid flow and results in renal failure. In the present study, we used the yeast two-hybrid system to determine the site of interaction of light chains with THP. The third complementarity-determining region (CDR3) of both kappa and lambda light chains interacted with THP. These findings were confirmed in a series of competition studies using a synthetic peptide that corresponded to the CDR3 region and purified THP and light chains. Variations in the CDR3 sequence of the light chain affected binding. Thus, the current studies increase our understanding of the process of cast formation and provide an opportunity to develop strategies that may inhibit this interaction and prevent the clinical manifestations of myeloma kidney.
管型肾病，即骨髓瘤肾病，是慢性肾衰竭的一个潜在可逆病因。在这种情况下，滤过的轻链与Tamm-Horsfall蛋白（THP）上的一个共同位点结合，THP由亨利氏袢升支粗段的细胞产生：这些蛋白随后聚集形成管型，阻塞肾小管液流动，导致肾衰竭。在本研究中，我们使用酵母双杂交系统来确定轻链与THP的相互作用位点。κ和λ轻链的第三个互补决定区（CDR3）均与THP相互作用。使用对应于CDR3区域的合成肽以及纯化的THP和轻链进行的一系列竞争研究证实了这些发现。轻链CDR3序列的变异影响结合。因此，当前的研究增进了我们对管型形成过程的理解，并提供了一个机会来制定可能抑制这种相互作用并预防骨髓瘤肾病临床表现的策略。
