Fei-Man Hsu, Rashmi P Mohanty, Liudmilla Rubbi, Michael Thompson, Harry Pickering, Elaine F Reed, John R Greenland, Joanna M Schaenman, Matteo Pellegrini
{"title":"An epigenetic human cytomegalovirus infection score predicts viremia risk in seropositive lung transplant recipients.","authors":"Fei-Man Hsu, Rashmi P Mohanty, Liudmilla Rubbi, Michael Thompson, Harry Pickering, Elaine F Reed, John R Greenland, Joanna M Schaenman, Matteo Pellegrini","doi":"10.1080/15592294.2024.2408843","DOIUrl":null,"url":null,"abstract":"<p><p>Cytomegalovirus (CMV) infection and reactivation in solid organ transplant (SOT) recipients increases the risk of viremia, graft failure and death. Clinical studies of CMV serostatus indicate that donor positive recipient negative (D<sup>+</sup>/R<sup>-</sup>) patients have greater viremia risk than D<sup>-</sup>/R<sup>-</sup>. The majority of patients are R<sup>+</sup> having intermediate serologic risk. To characterize the long-term impact of CMV infection and assess viremia risk, we sought to measure the effects of CMV on the recipient immune epigenome. Specifically, we profiled DNA methylation in 156 individuals before lung or kidney transplant. We found that the methylome of CMV positive SOT recipients is hyper-methylated at <i>loci</i> associated with neural development and Polycomb group (PcG) protein binding, and hypo-methylated at regions critical for the maturation of lymphocytes. In addition, we developed a machine learning-based model to predict the recipient CMV serostatus after correcting for cell type composition and ancestry. This CMV episcore measured at baseline in R<sup>+</sup> individual stratifies viremia risk accurately in the lung transplant cohort, and along with serostatus the CMV episcore could be a potential biomarker for identifying R<sup>+</sup> patients at high viremia risk.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2408843"},"PeriodicalIF":2.9000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451273/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Epigenetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/15592294.2024.2408843","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/3 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Cytomegalovirus (CMV) infection and reactivation in solid organ transplant (SOT) recipients increases the risk of viremia, graft failure and death. Clinical studies of CMV serostatus indicate that donor positive recipient negative (D+/R-) patients have greater viremia risk than D-/R-. The majority of patients are R+ having intermediate serologic risk. To characterize the long-term impact of CMV infection and assess viremia risk, we sought to measure the effects of CMV on the recipient immune epigenome. Specifically, we profiled DNA methylation in 156 individuals before lung or kidney transplant. We found that the methylome of CMV positive SOT recipients is hyper-methylated at loci associated with neural development and Polycomb group (PcG) protein binding, and hypo-methylated at regions critical for the maturation of lymphocytes. In addition, we developed a machine learning-based model to predict the recipient CMV serostatus after correcting for cell type composition and ancestry. This CMV episcore measured at baseline in R+ individual stratifies viremia risk accurately in the lung transplant cohort, and along with serostatus the CMV episcore could be a potential biomarker for identifying R+ patients at high viremia risk.
期刊介绍:
Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed.
Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to):
DNA methylation
Nucleosome positioning and modification
Gene silencing
Imprinting
Nuclear reprogramming
Chromatin remodeling
Non-coding RNA
Non-histone chromosomal elements
Dosage compensation
Nuclear organization
Epigenetic therapy and diagnostics
Nutrition and environmental epigenetics
Cancer epigenetics
Neuroepigenetics