An epigenetic human cytomegalovirus infection score predicts viremia risk in seropositive lung transplant recipients
Journal
Epigenetics
Journal Volume
19
Journal Issue
1
Start Page
2408843
ISSN
1559-2294
Date Issued
2024-10-03
Author(s)
Mohanty, Rashmi P.
Rubbi, Liudmilla
Thompson, Michael
Pickering, Harry
Reed, Elaine F.
Greenland, John R.
Schaenman, Joanna M.
Pellegrini, Matteo
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.
Subjects
biomarker
Cytomegalovirus
DNA methylation
epigenetics
kidney transplantation
lung transplantation
Publisher
Taylor and Francis Ltd.
Description
Article number 2408843
Type
journal article