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Influence of IFNL3/4 polymorphisms on the incidence of cytomegalovirus infection after solid-organ transplantation

Manuel, Oriol ; Wójtowicz, Agnieszka ; Bibert, Stéphanie ; Mueller, Nicolas J. ; van Delden, Christian ; Hirsch, Hans H. ; Steiger, Juerg ; Stern, Martin ; Egli, Adrian ; Garzoni, Christian ; Binet, Isabelle ; Weisser, Maja ; Berger, Christoph ; Cusini, Alexia ; Meylan, Pascal ; Pascual, Manuel ; Bochud, Pierre-Yves ; Binet, I. ; De Geest, S. ; van Delden, C. ; Hofbauer, GFK ; Huynh-Do, U. ; Koller, MT ; Lovis, C. ; Manuel, O. ; Meylan, P. ; Mueller, NJ ; Pascual, M. ; Schaub, S. ; Steiger, J.

In: The Journal of Infectious Diseases

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    Titre
    • Influence of IFNL3/4 polymorphisms on the incidence of cytomegalovirus infection after solid-organ transplantation
    Auteur
    • Manuel, Oriol. Infectious Diseases Service, Department of Medicine, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
    • Wójtowicz, Agnieszka. Infectious Diseases Service, Department of Medicine, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
    • Bibert, Stéphanie. Infectious Diseases Service, Department of Medicine, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
    • Mueller, Nicolas J.. Division of Infectious Diseases and Hospital Epidemiology, University Hospital, University of Zurich, Zürich, Switzerland
    • van Delden, Christian. Service of Transplantation, Department of Surgery, University Hospitals of Geneva, Geneva, Switzerland
    • Hirsch, Hans H.. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
    • Steiger, Juerg. Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland
    • Stern, Martin. Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel, Basel, Switzerland
    • Egli, Adrian. Clinical Microbiology, University Hospital Basel, Basel, Switzerland
    • Garzoni, Christian. Department of Infectious Diseases, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
    • Binet, Isabelle. Division of Nephrology and Transplantation Medicine, Kantonsspital St. Gallen, St. Gallen, Switzerland
    • Weisser, Maja. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
    • Berger, Christoph. Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital, Zurich, Switzerland
    • Cusini, Alexia. Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese, Lugano, Switzerland
    • Meylan, Pascal. Infectious Diseases Service, Department of Medicine, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
    • Pascual, Manuel. Transplantation Center, Department of Surgery, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
    • Bochud, Pierre-Yves. Infectious Diseases Service, Department of Medicine, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
    • Binet, I.
    • De Geest, S.
    • van Delden, C.
    • Hofbauer, GFK
    • Huynh-Do, U.
    • Koller, MT
    • Lovis, C.
    • Manuel, O.
    • Meylan, P.
    • Mueller, NJ
    • Pascual, M.
    • Schaub, S.
    • Steiger, J.
    Type de document
    • Postprint
    Classification
    • Santé
    Identifiant OAI-PMH
    • oai:doc.rero.ch:291711
    Summary
    Background. Polymorphisms in the interferon-λ (IFNL) 3/4 region have been associated with reduced hepatitis C virus clearance. We explored the role of such polymorphisms on the incidence of CMV infection in solid-organ transplant (SOT) recipients. Methods. Caucasian patients participating in the Swiss Transplant Cohort Study in 2008-2011 were included. A novel functional TT/-G polymorphism (rs368234815) in the CpG region upstream of IFNL3 was investigated. Results. A total of 840 SOT recipients at risk for CMV were included, among whom 373 (44%) received antiviral prophylaxis. The 12-months cumulative incidence of CMV replication and disease were 0.44 and 0.08, respectively. Patient homozygous for the minor rs368234815 allele (-G/-G) tended to have a higher cumulative incidence of CMV replication (SHR=1.30 [95%CI 0.97-1.74], P=0.07) compared to other patients (TT/TT or TT/-G). The association was significant among patients followed by a preemptive approach (SHR=1.46 [1.01-2.12], P=0.047), especially in patients receiving an organ from a seropositive donor (D+, SHR=1.92 [95%CI 1.30-2.85], P=0.001), but not among those who received antiviral prophylaxis (SHR=1.13 [95%CI 0.70-1.83], P=0.6). These associations remained significant in multivariate competing risk regression models. Conclusions. Polymorphisms in the IFNL3/4 region influence susceptibility to CMV replication in SOT recipients, particularly in patients not receiving antiviral prophylaxis