Serological evidence for reactivation of EBV infection due to uraemic immunodeficiency

BACKGROUND: Reactivation of EBV infection is a common finding in immunocompromised individuals. The influence of 'uraemic immunodeficiency' on EBV infection is so far not well defined. METHODS: We determined specific antibodies to EBV nuclear antigens (EBNA) 1 and 2 in sera of 286 patients with immunodeficiency due to progressive chronic renal failure and of 51 healthy controls. We used the baculovirus vector expression system for recombinant production of EBNA1 and EBNA2. RESULTS: Serological evidence of reactivated or chronic persistent EBV infection, i.e. an anti-EBNA1/anti-EBNA2 ratio (E1/E2) < 1, was found in 18% of patients with chronic renal failure not yet receiving renal replacement therapy (CRF), 11% of peritoneal dialysis patients (CAPD), 25% of haemodialysis patients (HD), 24% of renal transplant recipients (TX), and in 6% of healthy controls. Rate of EBV reactivation was significantly increased in HD (P = 0.004) and TX (P = 0.006) patients compared to healthy controls. Moreover, the difference between HD and CAPD patients was statistically significant (P < 0.05). This finding may reflect additional effects modulating the function of the immunosystem, probably through activation of immunologically competent cells by contact with the artificial surfaces of dialysis membranes. Although the rate of EBV reactivations is expected to increase further under conditions of therapeutic immunosuppression, our serological approach did not detect an additional effect of immunosuppressive therapy following renal transplantation. However, this finding may reflect an impaired endogenous synthesis of antibodies caused by immunosuppressive agents. CONCLUSIONS: We conclude that determination of E1/E2 is useful for assessment of EBV infection in patients with chronic renal failure and 'uraemic immunodeficiency'. In patients with immunosuppressive therapy following renal transplantation additional testing including direct estimation of viral load, is necessary to correctly assess the state of EBV infection.