Abstract
Granzyme B (GrB) is a serine protease released by cytotoxic T cells and plays a role in cellular apoptosis in cooperation with perforin. Recently however, extracellular roles of GrB have been reported. In particular, GrB accumulates in extracellular tissue and contributes to the loss of structural integrity in a number of chronic inflammatory, autoimmune, and degenerative diseases. Furthermore, GrB in vitro has the ability to cleave extracellular matrix components such as laminin and vitronectin, which constitute the glomerular basement membrane (GBM). Although, whether or not extracellular GrB mediates the pathogenesis of pediatric idiopathic nephrotic syndrome (INS) has not been reported to date. Here we performed flowcytometric analysis on the expression of GrB in peripheral blood mononuclear cells in patients with INS and showed a significantly higher ratio of GrB-positive cells to CD3-positive T cells in steroid-resistant nephritic syndrome patients. As an additional pathogenesis of glomerulosclerosis in INS, we considered that GrB might play a role in the injury of the glomerular filtration wall by detaching endothelial cells or podocytes from the GBM.
