Increased incidence of herpes zoster in patients on renal replacement therapy cannot be explained by intrinsic defects of cellular or humoral immunity to varicella-zoster virus

BACKGROUND: Patients in need of long-term renal replacement therapy (RRT) are known to be at increased risk of herpes zoster, occurring when the latently present varicella-zoster virus (VZV) reactivates. In this study we investigated immunity to VZV in patients receiving RRT, with the aim of better understanding the mechanism behind the increased risk. METHODS: Patients treated for at least three months with hemodialysis or peritoneal dialysis, and matched healthy controls (HC) were included. Cellular immunity to varicella-zoster virus (VZV) was studied using an interferon-γ (IFNγ) enzyme-linked immunospot (ELISpot) assay, flow-cytometric analysis of cytokine production and a proliferation assay. Humoral immunity was determined by measuring immunoglobulin (Ig)G antibody levels to VZV using an in-house glycoprotein enzyme-linked immunosorbent assay (ELISA). Multiple regression was used to assess variables of influence on measures of cellular and humoral immunity to VZV in patients receiving RRT. RESULTS: Similar numbers of IFNγ spot-forming cells and levels of VZV-IgG were found in 97 patients and 89 HC. Age and transplantation history were negatively associated with cellular immunity (p = 0.001 and p = 0.012, respectively) while treatment modality, gender and urea levels were not. No variables were found to be associated with VZV-IgG levels. CONCLUSIONS: Increased incidence of herpes zoster in patients receiving RRT cannot be explained by intrinsic defects of cellular or humoral immunity to VZV as measured by the methods used in this study, although older age and previous transplantation were associated with decreased cellular immunity to VZV. Herpes zoster susceptibility might be caused by a diminished function of otherwise capable T cells in a uremic environment