Frontiers in Immunology (Aug 2022)

Polygenic Innate Immunity Score to Predict the Risk of Cytomegalovirus Infection in CMV D+/R- Transplant Recipients. A Prospective Multicenter Cohort Study

  • Marta Bodro,
  • Carlos Cervera,
  • Laura Linares,
  • Belén Suárez,
  • Jaume Llopis,
  • Gemma Sanclemente,
  • Sergi Casadó-Llombart,
  • Mario Fernández-Ruiz,
  • María Carmen Fariñas,
  • Sara Cantisan,
  • Miguel Montejo,
  • Elisa Cordero,
  • Elisa Cordero,
  • Elisa Cordero,
  • Isabel Oriol,
  • María Angeles Marcos,
  • Francisco Lozano,
  • Francisco Lozano,
  • Francisco Lozano,
  • Asunción Moreno,
  • GESITRA-IC/SEIMC/REIPI investigators

DOI
https://doi.org/10.3389/fimmu.2022.897912
Journal volume & issue
Vol. 13

Abstract

Read online

Several genetic polymorphisms of the innate immune system have been described to increase the risk of cytomegalovirus (CMV) infection in transplant patients. The aim of this study was to assess the impact of a polygenic score to predict CMV infection and disease in high risk CMV transplant recipients (heart, liver, kidney or pancreas). On hundred and sixteen CMV-seronegative recipients of grafts from CMV-seropositive donors undergoing heart, liver, and kidney or pancreas transplantation from 7 centres were prospectively included for this purpose during a 2-year period. All recipients received 100-day prophylaxis with valganciclovir. CMV infection occurred in 61 patients (53%) at 163 median days from transplant, 33 asymptomatic replication (28%) and 28 CMV disease (24%). Eleven patients (9%) had recurrent CMV infection. Clinically and/or functionally relevant single nucleotide polymorphisms (SNPs) from TLR2, TLR3, TLR4, TLR7, TLR9, AIM2, MBL2, IL28, IFI16, MYD88, IRAK2 and IRAK4 were assessed by real time polymerase chain reaction (RT-PCR) or sequence-based typing (PCR-SBT). A polygenic score including the TLR4 (rs4986790/rs4986791), TLR9 (rs3775291), TLR3 (rs3775296), AIM2 (rs855873), TLR7 (rs179008), MBL (OO/OA/XAO), IFNL3/IL28B (rs12979860) and IFI16 (rs6940) SNPs was built based on the risk of CMV infection and disease. The CMV score predicted the risk of CMV disease with an AUC of the model of 0.68, with sensitivity and specificity of 64.3 and 71.6%, respectively. Even though further studies are needed to validate this score, its use would represent an effective model to develop more robust scores predicting the risk of CMV disease in donor/recipient mismatch (D+/R-) transplant recipients.

Keywords