Impacts of Interleukin-18 Polymorphisms on the Incidence of Delayed-Onset Cytomegalovirus Infection in a Cohort of Kidney Transplant Recipients

Isabel Pérez-Flores; Jose Luis Santiago; Cristina Fernández-Pérez; Elena Urcelay; María Ángeles Moreno de la Higuera; Natividad Calvo Romero; Beatriz Rodríguez Cubillo; Ana Isabel Sánchez-Fructuoso

doi:10.1093/ofid/ofz325

Impacts of Interleukin-18 Polymorphisms on the Incidence of Delayed-Onset Cytomegalovirus Infection in a Cohort of Kidney Transplant Recipients

Open Forum Infect Dis. 2019 Jul 20;6(9):ofz325. doi: 10.1093/ofid/ofz325. eCollection 2019 Sep.

Authors

Isabel Pérez-Flores¹, Jose Luis Santiago², Cristina Fernández-Pérez³, Elena Urcelay², María Ángeles Moreno de la Higuera¹, Natividad Calvo Romero¹, Beatriz Rodríguez Cubillo¹, Ana Isabel Sánchez-Fructuoso¹

Affiliations

¹ Nephrology Department, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain.
² Kidney Transplant Group Hospital Clínico San Carlos, Madrid, Spain.
³ Clinical Research and Methodology Unit, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos, Madrid, Spain.

Abstract

Background: The incidence of cytomegalovirus (CMV) infection in solid organ transplant recipients may be reduced by antiviral prophylaxis, but this strategy may lead to delayed-onset CMV infection. The proinflammatory cytokine interleukin (IL)-18 plays a major role in viral host defense responses. This study examines the impacts of 2 single-nucleotide polymorphisms (SNPs) in the promoter region of the IL-18 gene, -607C/A (rs1946518) and -137G/C (rs187238), on the incidence of delayed-onset CMV infection in patients undergoing kidney transplant.

Methods: This retrospective study analyzed 2 IL-18 SNPs in consecutive adult kidney transplant recipients using real-time polymerase chain reaction with TaqMan probes. Participants were enrolled over the period 2005-2013 and stratified according to their IL-18 SNP genotype. The concordance index (Harrell's c-index) was used as a measure of the discriminatory power of the predictive models constructed with bootstrapping to correct for optimistic bias.

Results: Seven hundred nine patients received transplants in the study period, and 498 met selection criteria. Cytomegalovirus infection and disease incidence were 38% and 7.5%, respectively. In multivariate competing risk regression models, carriers of the -607C/-137G haplotype who received prophylaxis showed a higher incidence of CMV replication after antiviral agent discontinuation (hazard ratio = 2.42 [95% confidence interval, 1.11-5.26]; P = .026), whereas CMV disease was not observed in those given prophylaxis who were noncarriers of this polymorphism (P = .009).

Conclusions: Our findings suggest that the -607C/-137G IL-18 haplotype is associated with a higher incidence of postprophylaxis CMV replication. The prior identification of this polymorphism could help select alternative measures to prevent delayed-onset CMV infection in these patients.

Keywords: IL-18 polymorphism; cohort study; delayed-onset cytomegalovirus infection; kidney transplant.