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Human Leukocyte Antigen-Based Risk Stratification in Heart Transplant Recipients-Implications for Targeted Surveillance

Nilsson, Johan LU orcid ; Ansari, David LU ; Ohlsson, Mattias LU orcid ; Höglund, Peter LU ; Liedberg, Ann Sofie LU ; Smith, J. Gustav LU ; Nugues, Pierre LU orcid and Andersson, Bodil LU orcid (2019) In Journal of the American Heart Association 8(15).
Abstract

Background Human leukocyte antigen (HLA) matching isn't routinely performed in heart transplantation. Novel allograft perfusion methods may make HLA matching feasible. The purpose of this study is to reexamine whether HLA mismatch may be used in risk stratification to improve outcomes in heart transplantation. Methods and Results We analyzed 34 681 recipients undergoing heart transplantation between 1987 and 2013. We used HLAMatchmaker to quantify HLA eplet mismatches and Cox regression for analysis of time to graft loss. Recipients with 4 mismatched HLA-DR/DQ alleles and >40 eplets reached an adjusted hazard ratio (HR) for graft loss of 1.17 (95% CI 1.07-1.28) and 1.11 (95% CI 1.03-1.21), respectively. We found significant... (More)

Background Human leukocyte antigen (HLA) matching isn't routinely performed in heart transplantation. Novel allograft perfusion methods may make HLA matching feasible. The purpose of this study is to reexamine whether HLA mismatch may be used in risk stratification to improve outcomes in heart transplantation. Methods and Results We analyzed 34 681 recipients undergoing heart transplantation between 1987 and 2013. We used HLAMatchmaker to quantify HLA eplet mismatches and Cox regression for analysis of time to graft loss. Recipients with 4 mismatched HLA-DR/DQ alleles and >40 eplets reached an adjusted hazard ratio (HR) for graft loss of 1.17 (95% CI 1.07-1.28) and 1.11 (95% CI 1.03-1.21), respectively. We found significant interaction between recipient age and numbers of HLA-DR/DQ allele and eplet mismatches resulting in an adjusted HR of 1.78 (95% 1.13-2.80) and 1.82 (95% CI, 1.23-2.70), respectively. HR for both interaction terms was 0.99 (95% CI, 0.98-1.00). Risk of graft loss was more pronounced after 1 year, where recipient <40 years with 4 mismatched HLA-DR/DQ alleles and >40 eplets had an adjusted HR of 1.51 (95% CI 1.12-2.03) and 1.32 (95% CI 1.02-1.70), respectively. Pre-sensitized recipients with panel reactive antibodies >10% had an adjusted HR=1.27 (95% CI 1.16-1.40) for graft loss within 1 year but not thereafter. HLA eplet mismatch was independent of panel reactive antibodies on reduction of graft loss within and after 1 year, P (interaction)=0.888 and 0.389. Conclusions HLA mismatch may be used in risk stratification for intensified post-transplant surveillance and therapy.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
HLAMatchmaker, human leukocyte antigen, rejection, risk stratification, survival, transplantation
in
Journal of the American Heart Association
volume
8
issue
15
article number
e011124
publisher
Wiley-Blackwell
external identifiers
  • pmid:31339067
  • scopus:85070483174
ISSN
2047-9980
DOI
10.1161/JAHA.118.011124
language
English
LU publication?
yes
id
e2550f48-1518-46ca-a1ab-b9ad05f4b47d
date added to LUP
2019-08-30 13:52:37
date last changed
2024-04-30 19:39:04
@article{e2550f48-1518-46ca-a1ab-b9ad05f4b47d,
  abstract     = {{<p>Background Human leukocyte antigen (HLA) matching isn't routinely performed in heart transplantation. Novel allograft perfusion methods may make HLA matching feasible. The purpose of this study is to reexamine whether HLA mismatch may be used in risk stratification to improve outcomes in heart transplantation. Methods and Results We analyzed 34 681 recipients undergoing heart transplantation between 1987 and 2013. We used HLAMatchmaker to quantify HLA eplet mismatches and Cox regression for analysis of time to graft loss. Recipients with 4 mismatched HLA-DR/DQ alleles and &gt;40 eplets reached an adjusted hazard ratio (HR) for graft loss of 1.17 (95% CI 1.07-1.28) and 1.11 (95% CI 1.03-1.21), respectively. We found significant interaction between recipient age and numbers of HLA-DR/DQ allele and eplet mismatches resulting in an adjusted HR of 1.78 (95% 1.13-2.80) and 1.82 (95% CI, 1.23-2.70), respectively. HR for both interaction terms was 0.99 (95% CI, 0.98-1.00). Risk of graft loss was more pronounced after 1 year, where recipient &lt;40 years with 4 mismatched HLA-DR/DQ alleles and &gt;40 eplets had an adjusted HR of 1.51 (95% CI 1.12-2.03) and 1.32 (95% CI 1.02-1.70), respectively. Pre-sensitized recipients with panel reactive antibodies &gt;10% had an adjusted HR=1.27 (95% CI 1.16-1.40) for graft loss within 1 year but not thereafter. HLA eplet mismatch was independent of panel reactive antibodies on reduction of graft loss within and after 1 year, P (interaction)=0.888 and 0.389. Conclusions HLA mismatch may be used in risk stratification for intensified post-transplant surveillance and therapy.</p>}},
  author       = {{Nilsson, Johan and Ansari, David and Ohlsson, Mattias and Höglund, Peter and Liedberg, Ann Sofie and Smith, J. Gustav and Nugues, Pierre and Andersson, Bodil}},
  issn         = {{2047-9980}},
  keywords     = {{HLAMatchmaker; human leukocyte antigen; rejection; risk stratification; survival; transplantation}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{15}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of the American Heart Association}},
  title        = {{Human Leukocyte Antigen-Based Risk Stratification in Heart Transplant Recipients-Implications for Targeted Surveillance}},
  url          = {{http://dx.doi.org/10.1161/JAHA.118.011124}},
  doi          = {{10.1161/JAHA.118.011124}},
  volume       = {{8}},
  year         = {{2019}},
}