Genomic Mismatch at
Adaptor Proteins, Signal Transducing
/ genetics
Cohort Studies
DNA Copy Number Variations
Genetic Association Studies
Genotype
Graft Rejection
/ genetics
HLA Antigens
/ genetics
Histocompatibility Testing
Humans
Immunoglobulin G
/ blood
Kidney Transplantation
LIM Domain Proteins
/ genetics
Membrane Proteins
/ genetics
Polymorphism, Single Nucleotide
Tissue Donors
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
16 05 2019
16 05 2019
Historique:
entrez:
16
5
2019
pubmed:
16
5
2019
medline:
29
5
2019
Statut:
ppublish
Résumé
In the context of kidney transplantation, genomic incompatibilities between donor and recipient may lead to allosensitization against new antigens. We hypothesized that recessive inheritance of gene-disrupting variants may represent a risk factor for allograft rejection. We performed a two-stage genetic association study of kidney allograft rejection. In the first stage, we performed a recessive association screen of 50 common gene-intersecting deletion polymorphisms in a cohort of kidney transplant recipients. In the second stage, we replicated our findings in three independent cohorts of donor-recipient pairs. We defined genomic collision as a specific donor-recipient genotype combination in which a recipient who was homozygous for a gene-intersecting deletion received a transplant from a nonhomozygous donor. Identification of alloantibodies was performed with the use of protein arrays, enzyme-linked immunosorbent assays, and Western blot analyses. In the discovery cohort, which included 705 recipients, we found a significant association with allograft rejection at the We found that the
Sections du résumé
BACKGROUND
In the context of kidney transplantation, genomic incompatibilities between donor and recipient may lead to allosensitization against new antigens. We hypothesized that recessive inheritance of gene-disrupting variants may represent a risk factor for allograft rejection.
METHODS
We performed a two-stage genetic association study of kidney allograft rejection. In the first stage, we performed a recessive association screen of 50 common gene-intersecting deletion polymorphisms in a cohort of kidney transplant recipients. In the second stage, we replicated our findings in three independent cohorts of donor-recipient pairs. We defined genomic collision as a specific donor-recipient genotype combination in which a recipient who was homozygous for a gene-intersecting deletion received a transplant from a nonhomozygous donor. Identification of alloantibodies was performed with the use of protein arrays, enzyme-linked immunosorbent assays, and Western blot analyses.
RESULTS
In the discovery cohort, which included 705 recipients, we found a significant association with allograft rejection at the
CONCLUSIONS
We found that the
Identifiants
pubmed: 31091373
doi: 10.1056/NEJMoa1803731
pmc: PMC6589355
mid: NIHMS1529617
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
HLA Antigens
0
Immunoglobulin G
0
LIM Domain Proteins
0
LIMS1 protein, human
0
Membrane Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1918-1928Subventions
Organisme : NCRR NIH HHS
ID : S10 RR027050
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007954
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_15025
Pays : United Kingdom
Organisme : NCATS NIH HHS
ID : UL1TR001873
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA013696
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001873
Pays : United States
Organisme : NIDDK NIH HHS
ID : T35 DK093430
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_16018
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : T32 DK108741
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 Massachusetts Medical Society.
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