Autoantibodies specific for the phospholipase A2 receptor in recurrent and De Novo membranous nephropathy.

Recent findings in idiopathic membranous nephropathy (MN) suggest that in most patients, the disease is because of anti-phospholipase A(2) receptor (PLA(2) R1) autoantibodies. Our aim was to analyze the prevalence and significance of anti-PLA(2) R1 antibodies in recurrent and de novo MN after transplantation. We assessed circulating PLA(2) R1 autoantibodies by a direct immunofluorescence assay based on human embryonic kidney cells transfected with a PLA(2) R1 cDNA, and the presence of PLA(2) R1 antigen in immune deposits. We showed that PLA(2) R1 was involved in 5 of 10 patients with recurrent MN, but in none of the 9 patients with de novo MN. We also showed a marked heterogeneity in the kinetics and titers of anti-PLA(2) R1, which may relate to different pathogenic potential. We provide evidence that some patients with PLA(2) R1-related idiopathic MN and anti-PLA(2) R1 antibodies at the time of transplantation will not develop recurrence. Because PLA(2) R1 autoantibody was not always associated with recurrence, its predictive value should be carefully analyzed in prospective studies.

Hemodialysis reduces plasma apolipoprotein C-I concentration making VLDL a better substrate for lipoprotein lipase.

Apolipoprotein Cs (apoC-1, apoC-II, and apoC-III) are lipoprotein components that have regulatory effects on enzymes involved in lipoprotein metabolism. Owing to their low molecular weights, apoCs can adsorb onto and/or pass through dialysis membranes. Our study determines the consequence of hemodialysis (HD) on plasma concentrations of apoCs and on the activities of enzymes modulated by apoCs. Plasma samples were collected from 28 patients with chronic renal failure before and after HD. Plasma apoC-II levels were unchanged, whereas apoC-III levels were slightly decreased in post-dialysis plasmas. The apoC-I content was markedly reduced during HD. This was due to a significant decrease in the apoC-I content of very low-density lipoprotein (VLDL), whereas the apoC-I content of high-density lipoprotein (HDL) was unchanged. Although HDL bound apoC-I is thought to inhibit cholesterol ester transfer protein, no change in the ability of pre- and post-dialysis VLDL to interact with the transfer protein were observed. Complementary experiments confirmed that VLDL-bound apoC-I has no transfer protein inhibitory potential. In contrast, an increase in the ability of post-dialysis apoC-I-poor VLDL to act as substrate for lipoprotein lipase (LPL) was found compared to pre-dialysis VLDL. Our study shows that apoC-I losses during HD might be beneficial by improving the ability of VLDL to be a substrate for LPL thus improving plasma triglyceride metabolism.

Human seminal plasma displays significant phospholipid transfer activity due to the presence of active phospholipid transfer protein.

The lipid composition of germ cell membranes is considerably modified during spermatogenesis, sperm maturation and capacitation. Some of these modifications are caused by exchanges between soluble lipid donors or acceptors and cell membranes. The aim of this study was to assess whether significant lipid transfers between lipoprotein structures are detectable in human seminal plasma. Phospholipid and cholesteryl ester (CE) transfer activities were measured by specific fluorescence and isotopic assays. Seminal plasma samples did not display significant CE transfer. Substantial levels of phospholipid transfer activity were detected in all samples studied, levels were approximately 25% of the phospholipid transfer activity measured in human blood plasma. Concordantly, CE transfer protein was not detected in seminal plasma, while the presence of the phospholipid transfer protein (PLTP) was confirmed by Western blot analysis. Enzyme-linked immunosorbent assay indicated that seminal PLTP concentrations represented 25% of the concentration measured in blood plasma. Blockade of phosphatidylcholine and phosphatidyl-ethanolamine transfer by a 60 min, 56 degrees C heating step or with anti-PLTP antibody revealed that PLTP accounts for almost 80% of the phospholipid transfer activity present in seminal plasma. As shown by gel-permeation chromatography and Western blot analysis, seminal PLTP activity was partially associated with prostasomes. Significantly higher PLTP activity levels were measured in seminal plasma samples with low seminal vesicle secretions. The latter observation may reflect the sustained secretion of active PLTP that is diluted in a variable volume of PLTP-free seminal vesicle secretion. In conclusion, human seminal plasma displays significant phospholipid transfer activity due to the presence of active PLTP.