CTLA4 Single-Nucleotide Polymorphisms Influence the Risk of HSV and VZV Infection in Kidney Transplant Recipients: A Prospective Cohort Study.

Abstract

Herpesviruses are able to modulate adaptive T-cell-mediated responses to establish latency within the host. Reactivation of herpes simplex virus (HSV)-1/2 and varicella zoster virus (VZV) is a frequent and potentially serious complication among kidney transplant recipients (KTRs). The ability of clinical criteria to identify KTRs at increased risk of α-herpesvirus (HSV/VZV) infection is limited. We investigated the effect of two single nucleotide polymorphisms (SNPs) in the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene in a single-center cohort of 204 KTRs. After a median follow-up of 3.1 years, 34 of them (16.7%) experienced 22 episodes of zoster and 15 episodes of HSV-1/2 infection. Homozygous carriers of the minor allele of rs231775 had a higher cumulative incidence of α-herpesvirus infection (23.5% for GG versus 7.6% for AA/AG carriers; P-value = 0.011) and a lower infection-free survival (log-rank P-value = 0.037). After multivariable adjustment by clinical factors (including use of valganciclovir prophylaxis and acute rejection as time-dependent variables), the GG genotype of CTLA4 (rs231775) SNP was associated to the study outcome (adjusted hazard ratio: 3.21; 95% confidence interval: 1.44-7.16). In conclusion, genetic polymorphisms in the co-inhibitory T-cell receptor CTLA-4 may be detrimental for the immune control of latent HSV/VZV infection in KTRs.