PMID- 34169197
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220424
IS  - 2468-0249 (Electronic)
IS  - 2468-0249 (Linking)
VI  - 6
IP  - 6
DP  - 2021 Jun
TI  - On Path to Informing Hierarchy of Eplet Mismatches as Determinants of Kidney 
      Transplant Loss.
PG  - 1567-1579
LID - 10.1016/j.ekir.2021.03.877 [doi]
AB  - INTRODUCTION: To mitigate risks related to human leukocyte antigen (HLA) 
      incompatibility, we assessed whether certain structurally defined HLA targets 
      present in donors but absent from recipients, known as eplet mismatches (EMM), 
      are associated with death-censored graft failure (DCGF). METHODS: We studied a 
      cohort of 118,313 American 0% panel reactive antibodies (PRA) first kidney 
      transplant recipients (2000 to 2015) from the Scientific Registry of Transplant 
      Recipients. Imputed allele-level donor and recipient HLA-A, -B, -C, -DRB1, and 
      -DQB1 genotypes were converted to the repertoire of EMM. We fit survival models 
      for each EMM with significance thresholds corrected for false discovery rate and 
      validated those in an independent PRA > 0% cohort. We conducted network-based 
      analyses to model relationships among EMM and developed models to select the 
      subset of EMM most predictive of DCGF. RESULTS: Of 412 EMM observed, 119 class I 
      and 118 class II EMM were associated with DCGF. Network analysis showed that 
      although 210 eplets formed profiles of 2 to 12 simultaneously occurring EMMs, 202 
      were singleton EMMs that were not involved in any profile. A variable selection 
      procedure identified 55 single HLA class I and II EMMs in 70% of the dataset; of 
      those, 15 EMMs (9 singleton and 6 involved in profiles) were predictive of DCGF 
      in the remaining dataset. CONCLUSION: Our analysis distinguished increasingly 
      smaller subsets of EMMs associated with increased risk of DCGF. Validation of 
      these EMMs as important predictors of transplant outcomes (in contrast to 
      acceptable EMMs) in datasets with measured allele-level genotypes will support 
      their role as immunodominant EMMs worthy of consideration in organ allocation 
      schemes.
CI  - (c) 2021 International Society of Nephrology. Published by Elsevier Inc.
FAU - Mohammadhassanzadeh, Hossein
AU  - Mohammadhassanzadeh H
AD  - Centre for Outcomes Research and Evaluation, Research Institute of McGill 
      University Health Centre, Montreal, Quebec, Canada.
FAU - Oualkacha, Karim
AU  - Oualkacha K
AD  - Department of Mathematics, University of Quebec in Montreal, Montreal, Quebec, 
      Canada.
FAU - Zhang, Wenmin
AU  - Zhang W
AD  - Quantitative Life Sciences, McGill University, Montreal, Quebec, Canada.
FAU - Klement, William
AU  - Klement W
AD  - Centre for Outcomes Research and Evaluation, Research Institute of McGill 
      University Health Centre, Montreal, Quebec, Canada.
AD  - Canadian Blood Services, Ottawa, Ontario, Canada.
FAU - Bourdiec, Amelie
AU  - Bourdiec A
AD  - Centre for Outcomes Research and Evaluation, Research Institute of McGill 
      University Health Centre, Montreal, Quebec, Canada.
FAU - Lamsatfi, Jennat
AU  - Lamsatfi J
AD  - Department of Mathematics, University of Quebec in Montreal, Montreal, Quebec, 
      Canada.
FAU - Yi, Yang
AU  - Yi Y
AD  - Department of Mathematics and Statistics, McGill University, Montreal, Quebec, 
      Canada.
FAU - Foster, Bethany
AU  - Foster B
AD  - Centre for Outcomes Research and Evaluation, Research Institute of McGill 
      University Health Centre, Montreal, Quebec, Canada.
AD  - Department of Pediatrics, Montreal Children's Hospital of the McGill University 
      Health Centre, Montreal, Quebec, Canada.
FAU - Keown, Paul
AU  - Keown P
AD  - University of British Columbia, Vancouver, British Columbia, Canada.
FAU - Gebel, Howard M
AU  - Gebel HM
AD  - Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA.
FAU - Claas, Frans
AU  - Claas F
AD  - Department of Immunology, Leiden University Medical Centre, Leiden, Netherlands.
FAU - Sapir-Pichhadze, Ruth
AU  - Sapir-Pichhadze R
AD  - Centre for Outcomes Research and Evaluation, Research Institute of McGill 
      University Health Centre, Montreal, Quebec, Canada.
AD  - Division of Nephrology and Multi-Organ Transplant Program, Department of 
      Medicine, McGill University, Montreal, Quebec, Canada.
CN  - Genome Canada Transplant Consortium
LA  - eng
PT  - Journal Article
DEP - 20210330
PL  - United States
TA  - Kidney Int Rep
JT  - Kidney international reports
JID - 101684752
PMC - PMC8207474
OTO - NOTNLM
OT  - epitope
OT  - eplet
OT  - graft failure
OT  - human leukocyte antigens
OT  - immunogenicity
OT  - kidney transplantation
EDAT- 2021/06/26 06:00
MHDA- 2021/06/26 06:01
PMCR- 2021/03/30
CRDT- 2021/06/25 06:56
PHST- 2021/02/24 00:00 [received]
PHST- 2021/03/08 00:00 [accepted]
PHST- 2021/06/25 06:56 [entrez]
PHST- 2021/06/26 06:00 [pubmed]
PHST- 2021/06/26 06:01 [medline]
PHST- 2021/03/30 00:00 [pmc-release]
AID - S2468-0249(21)01024-X [pii]
AID - 10.1016/j.ekir.2021.03.877 [doi]
PST - epublish
SO  - Kidney Int Rep. 2021 Mar 30;6(6):1567-1579. doi: 10.1016/j.ekir.2021.03.877. 
      eCollection 2021 Jun.