Possible mechanisms of LDL apheresis for pediatric patients with steroid resistant and refractory nephrotic syndrome

Although the favorable therapeutic effects of LDL apheresis (LDL-A) have been widely reported in pediatric patients with steroid resistant and refractory nephrotic syndrome, the mechanism by which LDL-A benefits patients with SRNS is obscure. To clarify the exact mechanism of LDL-A, we analyzed the gene expression of peripheral blood mononuclear cells (PBMC) from LDL-A effective patients, using cDNA microarrays and real-time reverse transcription-polymerase chain reaction (RT-PCR). We conducted the extraction of the genes that are specifically related with favorable effects of LDL-A through the comparing of the gene expressions between nephrosis and complete remission phases, and GZMB encoding granzyme B was extracted out of the candidate genes. For further examination, polychromic flow cytometric analysis was performed to evaluate the expression of granzyme B in pan T cells from patients with steroid resistant nephrotic syndrome (SRNS), steroid sensitive nephrotic syndrome (SSNS) and healthy subjects. The percentage of granzyme B-positive T cells in SRNS patients was significantly higher than those in SSNS and healthy controls. In recent years, emerging clinical and biochemical evidence has shown that perforin-independent extracellular granzyme B may have a pathogenic role in several kinds of diseases. Our results indicated the possibilities that granzyme B expressed in circulating T cells might have pathogenic role for SRNS through the involvement of the glomerular filtration barrier and that a favorable regulation of granzyme B over-expression in T cells by LDL-A might be associated with a remission of steroid resistant and refractory nephrotic syndrome.