mAb 5-1-6 nephropathy and nephrin

It is well established that the glomerular capillary wall consists of three layers: endothelial cell, glomerular basement membrane, and the slit diaphragm bridging foot processes of glomerular epithelial cell. Which structure in the glomerular capillary wall represents the primary filter for retaining plasma proteins is not clearly elucidated. An anti-slit diaphragm monoclonal antibody (mAb) 5-1-6 causes massive proteinuria in rats by single intravenous injection, which clearly indicates that the slit diaphragm plays a critical role for maintaining the barrier function of the glomerular capillary wall. Recently, we concluded that mAb 5-1-6 recognized a rat homolog of nephrin, a gene product of NPHS1. The expression of nephrin decreased in puromycin aminonucleoside nephropathy and adriamycin nephropathy as well as mAb 5-1-6-induced nephropathy, which suggested that nephrin was involved in the development of proteinuria in these proteinuric states. In mAb 5-1-6 nephropathy, the slit diaphragm was maintained morphologically normal, although nephrin expression dramatically decreased. The finding suggested that nephrin was not a sole component of the slit diaphragm. To better understand the structure of the slit diaphragm, it is particularly important to identify other components that build up the structure of the slit diaphragm together with nephrin.