DNA methylation predicts infection risk in kidney transplant recipients
Journal
Life Science Alliance
Journal Volume
8
Journal Issue
7
Start Page
e202403124
ISSN
2575-1077
Date Issued
2025-05-05
Author(s)
Pickering, Harry
Rubbi, Liudmilla
Thompson, Michael
Reed, Elaine F
Pellegrini, Matteo
Schaenman, Joanna M
Abstract
Kidney transplantation (KTx) is the method of choice for treating kidney failure. Identifying biomarkers predictive of transplant (Tx) outcomes is critical to optimize KTx; however, the immunosuppressive therapies required after KTx must also be considered. We applied targeted bisulfite sequencing (TBS-seq) to PBMCs isolated from 90 patients, with samples collected pre-and post-Tx (day 90), to measure DNA methylation changes. Our findings indicate that the PBMC DNA methylome is significantly affected by induction immunosuppression with anti-thymocyte globulin (ATG). We discovered that the risk of infection can be predicted using DNA methylation profiles, but not gene expression profiles. Specifically, 515 CpG loci associated with 275 genes were significantly impacted by ATG induction, even after accounting for age, sex, and cell-type composition. Notably, ATG-associated hyper-methylation down-regulates genes critical for immune response. In conclusion, this clinical omics study reveals that the immunosuppressant ATG profoundly impacts the DNA methylome of KTx recipients and identifies biomarkers that could be used in pre-Tx screening of patients vulnerable to infection, thereby informing immunosuppression strategies post-Tx.
Subjects
biological marker
immunosuppressive agent
lymphocyte antibody
Publisher
Life Science Alliance
Description
Article number e202403124
Type
journal article