PT  - JOURNAL ARTICLE
AU  - Hsu, Fei-Man
AU  - Pickering, Harry
AU  - Rubbi, Liudmilla
AU  - Thompson, Michael
AU  - Reed, Elaine F
AU  - Pellegrini, Matteo
AU  - Schaenman, Joanna M
TI  - DNA methylation predicts infection risk in kidney transplant recipients
AID  - 10.26508/lsa.202403124
DP  - 2025 Jul 01
TA  - Life Science Alliance
PG  - e202403124
VI  - 8
IP  - 7
4099  - http://www.life-science-alliance.org/content/8/7/e202403124.short
4100  - http://www.life-science-alliance.org/content/8/7/e202403124.full
SO  - Life Sci. Alliance2025 Jul 01; 8
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.