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The association of hepatitis C virus (HCV) infection and glomerulonephritis is well known. However, the relationship between immune-mediated glomerulonephritis and occult HCV, characterized by the presence of HCV-RNA in liver or in peripheral blood mononuclear cells in the absence of serological markers, is unknown. We tested this in 113 anti-HCV-negative patients; 87 with immune-mediated glomerulonephritis and 26 controls with hereditary glomerular nephropathies. All patients were serum HCV-RNA negative by conventional real-time PCR. Significantly, occult HCV-RNA (detectable viral RNA in peripheral blood mononuclear cells or in serum after ultracentrifugation) was found in 34 of 87 patients with immune-mediated glomerulonephritis versus 1 of 26 control patients. The serum creatinine levels were significantly higher in patients with immune-mediated glomerulonephritis with than in those without occult HCV (1.5 versus 1.1 mg/dl, respectively). A multivariate analysis adjusted for gender showed a significantly increased risk of occult HCV in patients with immune-mediated glomerulonephritis versus the controls (odds ratio of 13.29). Progression to end-stage renal disease tended to be faster in patients with immune-mediated glomerulonephritis and occult HCV than in the negative cases. Thus, occult HCV is strongly associated with immune-mediated glomerulonephritis and may have a role in the progression of the disease. [ABSTRACT FROM AUTHOR]

The classical view of the immune system has changed by the discovery of novel T-helper (Th) subsets, including Th17 (IL-17A-producing cells). IL-17A participates in immune-mediated glomerulonephritis and more recently in inflammatory pathologies, including experimental renal injury. Peritoneal dialysis patients present chronic inflammation and Th1/Th2 imbalance, but the role of the Th17 response in peritoneal membrane damage has not been investigated. In peritoneal biopsies from dialyzed patients, IL-17A immunostaining was found mainly in inflammatory areas and was absent in the healthy peritoneum. IL-17A-expressing cells included lymphocytes (CD4+ and γδ), neutrophils, and mast cells. Elevated IL-17A effluent concentrations were found in long-term peritoneal dialysis patients. Studies in mice showed that repeated exposure to recombinant IL-17A caused peritoneal inflammation and fibrosis. Moreover, chronic exposure to dialysis fluids resulted in a peritoneal Th17 response, including elevated IL-17A gene and protein production, submesothelial cell infiltration of IL-17A-expressing cells, and upregulation of Th17 differentiation factors and cytokines. IL-17A neutralization diminished experimental peritoneal inflammation and fibrosis caused by chronic exposure to dialysis fluids in mice. Thus, IL-17A is a key player of peritoneum damage and it may be a good candidate for therapeutic intervention in peritoneal dialysis patients. [ABSTRACT FROM AUTHOR]

Regulation of apoptosis by lethal cytokines in human mesothelial cells. Background. Dysregulation of peritoneal cell death may contribute to the complications of peritoneal dialysis (PD). Chronic peritoneal dialysis and acute peritonitis are both associated with loss of mesothelial cells. In addition, acute peritonitis is characterized by sudden changes in the number of peritoneal leukocytes. However, the factors regulating peritoneal cell survival are poorly understood. Methods. Peritoneal effluent cells and mesothelial cells cultured from peritoneal dialysis patients were studied. Reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry were used to assess the expression of FasL and Fas mRNA and protein. Western blot was used to assess FasL and tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). RT-PCR was used to study TRAIL and TRAIL receptor mRNA. Apoptosis was quantified by flow cytometry of DNA content and confirmed by morphology. Results. Apoptotic cells, including apoptotic mesothelial cells, were present in the peritoneal effluent of stable peritoneal dialysis patients and patients with bacterial peritonitis. The lethal cytokines FasL and TRAIL were expressed by peritoneal effluent cells, while cultured mesothelial cells expressed FasL, Fas, and TRAIL receptors. Cultured mesothelial cells were sensitive to FasL-induced apoptosis. IFNγ increased the cell surface expression of Fas and the sensitivity of mesothelial cells to FasL-induced apoptosis. In contrast to the effect of FasL, TNFα and TRAIL did not induce apoptosis in human mesothelial cells from peritoneal dialysis patients. Conclusion. Lethal cytokines, such as FasL, may contribute to peritoneal cell turnover and the loss of mesothelium in peritoneal dialysis. The role of other cytokines, such as TRAIL, remains undefined. Approaches in limiting mesothelial cell injury that interferes with apoptosis should be considered. [ABSTRACT FROM AUTHOR]