Infectious Diseases Department, Hospital Clinic de Barcelona - Institut d' Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Department of Medicine, University of Alberta, Edmonton, AB, Canada.
Front Immunol. 2022 Aug 9;13:897912. doi: 10.3389/fimmu.2022.897912. eCollection 2022.
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 , , , , , , , , IFI16, , and were assessed by real time polymerase chain reaction (RT-PCR) or sequence-based typing (PCR-SBT). A polygenic score including the (rs4986790/rs4986791), (rs3775291), (rs3775296), (rs855873), (rs179008), (OO/OA/XAO), (rs12979860) and (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.
一些先天免疫系统的遗传多态性已被描述为增加移植患者巨细胞病毒 (CMV) 感染的风险。本研究旨在评估多基因评分对预测高危 CMV 移植受者（心脏、肝脏、肾脏或胰腺）CMV 感染和疾病的影响。在 7 个中心进行的为期 2 年的前瞻性研究中，共纳入 116 例 CMV 阴性受者，他们接受来自 CMV 阳性供者的心脏、肝脏、肾脏或胰腺移植。所有受者均接受为期 100 天的缬更昔洛韦预防治疗。163 天中位数后，61 例患者（53%）发生 CMV 感染，33 例无症状复制（28%）和 28 例 CMV 疾病（24%）。11 例（9%）患者发生复发性 CMV 感染。通过实时聚合酶链反应（RT-PCR）或基于序列的分型（PCR-SBT）评估 、 、 、 、 、 、IFI16 、 和 中与临床和/或功能相关的单核苷酸多态性（SNP）。根据 CMV 感染和疾病的风险，构建了一个包含 （rs4986790/rs4986791）、 （rs3775291）、 （rs3775296）、 （rs855873）、 （rs179008）、 （OO/OA/XAO）、 （rs12979860）和 （rs6940）SNP 的多基因评分。CMV 评分预测 CMV 疾病的风险，模型 AUC 为 0.68，敏感性和特异性分别为 64.3%和 71.6%。尽管需要进一步研究来验证该评分，但它的使用将代表一种有效的模型，用于开发更强大的评分，预测供体/受体不匹配（D+/R-）移植受者 CMV 疾病的风险。
