Fei-Man Hsu, Harry Pickering, Liudmilla Rubbi, Michael Thompson, Elaine F Reed, Matteo Pellegrini, Joanna M Schaenman
{"title":"DNA甲基化预测肾移植受者感染风险。","authors":"Fei-Man Hsu, Harry Pickering, Liudmilla Rubbi, Michael Thompson, Elaine F Reed, Matteo Pellegrini, Joanna M Schaenman","doi":"10.26508/lsa.202403124","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>loci</i> 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.</p>","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 7","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053434/pdf/","citationCount":"0","resultStr":"{\"title\":\"DNA methylation predicts infection risk in kidney transplant recipients.\",\"authors\":\"Fei-Man Hsu, Harry Pickering, Liudmilla Rubbi, Michael Thompson, Elaine F Reed, Matteo Pellegrini, Joanna M Schaenman\",\"doi\":\"10.26508/lsa.202403124\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 <i>loci</i> 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.</p>\",\"PeriodicalId\":18081,\"journal\":{\"name\":\"Life Science Alliance\",\"volume\":\"8 7\",\"pages\":\"\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-05-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053434/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Life Science Alliance\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.26508/lsa.202403124\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/7/1 0:00:00\",\"PubModel\":\"Print\",\"JCR\":\"Q1\",\"JCRName\":\"BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life Science Alliance","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.26508/lsa.202403124","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/1 0:00:00","PubModel":"Print","JCR":"Q1","JCRName":"BIOLOGY","Score":null,"Total":0}
DNA methylation predicts infection risk in kidney transplant recipients.
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.
期刊介绍:
Life Science Alliance is a global, open-access, editorially independent, and peer-reviewed journal launched by an alliance of EMBO Press, Rockefeller University Press, and Cold Spring Harbor Laboratory Press. Life Science Alliance is committed to rapid, fair, and transparent publication of valuable research from across all areas in the life sciences.