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

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

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.897912

DOI=10.3389/fimmu.2022.897912

ISSN=1664-3224

ABSTRACT=<p>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 <italic>TLR2</italic>, <italic>TLR3</italic>, <italic>TLR4</italic>, <italic>TLR7</italic>, <italic>TLR9</italic>, <italic>AIM2</italic>, <italic>MBL2</italic>, <italic>IL28</italic>, IFI16, <italic>MYD88</italic>, <italic>IRAK2</italic> and <italic>IRAK4</italic> were assessed by real time polymerase chain reaction (RT-PCR) or sequence-based typing (PCR-SBT). A polygenic score including the <italic>TLR4</italic> (rs4986790/rs4986791), <italic>TLR9</italic> (rs3775291), <italic>TLR3</italic> (rs3775296), <italic>AIM2</italic> (rs855873), <italic>TLR7</italic> (rs179008), <italic>MBL</italic> (OO/OA/XAO), <italic>IFNL3/IL28B</italic> (rs12979860) and <italic>IFI16</italic> (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.</p>