DNA Methylation Age Is More Closely Associated With Infection Risk Than Chronological Age in Kidney Transplant Recipients.
Journal
Transplantation direct
ISSN: 2373-8731
Titre abrégé: Transplant Direct
Pays: United States
ID NLM: 101651609
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
17
02
2020
revised:
03
04
2020
accepted:
07
04
2020
entrez:
2
11
2020
pubmed:
3
11
2020
medline:
3
11
2020
Statut:
epublish
Résumé
Older kidney transplant recipients demonstrate increased rates of infection but decreased rates of rejection compared with younger recipients, suggesting that older transplant patients are functionally overimmunosuppressed. We hypothesized that this is a consequence of reduction in immunological activity due to biological aging and that an immune biological age, as determined by DNA methylation (DNAm), would be associated more strongly with incidence of infection than chronological age. DNAm analysis was performed on peripheral blood mononuclear cell collected from 60 kidney transplant recipients representing older (≥age 60 y) and younger (aged 30-59 y) patients 3 months after transplantation. DNAm age was calculated based on methylation status of a panel of CpG sites, which have been previously identified as indicative of biological age. Correlation was seen between chronological and DNAm age; however, there were many patients with significant differences (either acceleration or slowing) between DNAm age and chronological age. A statistically significant association was seen between increased DNAm age and incidence of infection in the first year after kidney transplantation, whereas no significant association was seen between chronological age and infection. Assessment of DNAm age holds promise as an approach for patient evaluation and individualization of immune suppression regimens. This analysis may provide insights into the immunological mechanism behind increased incidence of infection observed in older transplant patients. The ability to measure biological age would allow for patient risk stratification and individualization of immunosuppression, improving outcomes for the growing numbers of older patients undergoing kidney transplantation.
Identifiants
pubmed: 33134500
doi: 10.1097/TXD.0000000000001020
pmc: PMC7581059
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e576Subventions
Organisme : NIA NIH HHS
ID : R03 AG050946
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG055879
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI128913
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001881
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
Références
BMC Genomics. 2012 Nov 17;13:636
pubmed: 23157493
Transplantation. 2009 Nov 15;88(9):1101-8
pubmed: 19898206
Transpl Int. 2013 Mar;26(3):242-53
pubmed: 23190423
Am J Transplant. 2016 Apr;16(4):1070-8
pubmed: 26780242
Bioessays. 2015 Jan;37(1):20-4
pubmed: 25303747
Nat Commun. 2015 Oct 22;6:8570
pubmed: 26490707
Eur J Cancer. 2017 Apr;75:299-307
pubmed: 28259012
Epigenomics. 2011 Dec;3(6):771-84
pubmed: 22126295
Clin Epigenetics. 2017 Feb 2;9:9
pubmed: 28168006
Hum Immunol. 2018 Sep;79(9):659-667
pubmed: 29913200
Transplantation. 2015 Nov;99(11):2258-68
pubmed: 26244716
Int Rev Immunol. 2014 May-Jun;33(3):162-73
pubmed: 24127845
Clin Transplant. 2009 Nov-Dec;23(6):930-7
pubmed: 19594773
Transplant Rev (Orlando). 2015 Oct;29(4):237-9
pubmed: 26411381
Transplant Direct. 2018 Feb 14;4(3):e348
pubmed: 29707619
Transplantation. 2016 Apr;100(4):705-6
pubmed: 26950715
Am J Transplant. 2012 Oct;12(10):2608-22
pubmed: 22958872
Immunol Lett. 2014 Nov;162(1 Pt B):310-5
pubmed: 25014741
Genome Biol. 2012 Oct 03;13(10):R97
pubmed: 23034122
J Heart Lung Transplant. 2016 Jul;35(7):843-50
pubmed: 27085975
Am J Kidney Dis. 2013 May;61(5):790-7
pubmed: 23261121
Nat Rev Immunol. 2009 Feb;9(2):91-105
pubmed: 19151746
Transplantation. 2005 Oct 15;80(7):989-92
pubmed: 16249750
Aging (Albany NY). 2016 Sep 28;8(9):1844-1865
pubmed: 27690265
Transplant Direct. 2019 Mar 04;5(4):e436
pubmed: 30993190
Aging Cell. 2015 Dec;14(6):924-32
pubmed: 25913071
Mech Ageing Dev. 2010 Feb;131(2):96-104
pubmed: 20060852
Genome Biol. 2013;14(10):R115
pubmed: 24138928
Am J Transplant. 2019 Apr;19(4):984-994
pubmed: 30506632
Methods. 2013 May 15;61(1):30-8
pubmed: 23583887
PLoS One. 2011;6(6):e14821
pubmed: 21731603