RT Journal Article
SR Electronic
T1 DNA methylation predicts infection risk in kidney transplant recipients
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202403124
DO 10.26508/lsa.202403124
VO 8
IS 7
A1 Hsu, Fei-Man
A1 Pickering, Harry
A1 Rubbi, Liudmilla
A1 Thompson, Michael
A1 Reed, Elaine F
A1 Pellegrini, Matteo
A1 Schaenman, Joanna M
YR 2025
UL http://www.life-science-alliance.org/content/8/7/e202403124.abstract
AB 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.TBS-seq and RNA-seq data from this study are deposited to Gene Expression Omnibus under the accession number GSE250536.Ethics declarationsEthics approval and consent to participateThe study procedures, informed consent, and data collection documents were reviewed and approved by the Institutional Review Board of the UCLA (IRB#11-001387). All procedures were conducted in accordance with the principles outlined in the Declaration of Helsinki.Consent for publicationInformed consent was obtained from all subjects involved in this study.