PMID- 31164432
OWN - NLM
STAT- MEDLINE
DCOM- 20200929
LR  - 20200929
IS  - 1399-3003 (Electronic)
IS  - 0903-1936 (Linking)
VI  - 54
IP  - 2
DP  - 2019 Aug
TI  - Donor human leukocyte antigen-G single nucleotide polymorphisms are associated 
      with post-lung transplant mortality.
LID - 1802126 [pii]
LID - 10.1183/13993003.02126-2018 [doi]
AB  - Human leukocyte antigen (HLA)-G is a non-classical HLA that inhibits immune 
      responses. Its expression is modified by single nucleotide polymorphisms (SNPs), 
      which are associated with transplant outcomes. Our aim was to investigate the 
      association of donor and recipient HLA-G SNPs with chronic lung allograft 
      dysfunction (CLAD) and mortality after lung transplantation.In this single-centre 
      study, we examined 11 HLA-G SNPs in 345 consecutive recipients and 297 donors of 
      a first bilateral lung transplant. A multivariable Cox proportional hazards model 
      assessed associations of SNPs with death and CLAD. Transbronchial biopsies (TBBx) 
      and bronchoalveolar lavage (BAL) samples were examined using quantitative PCR, 
      ELISA and immunofluorescence.Over a median of 4.75 years, 142 patients (41%) 
      developed CLAD; 170 (49%) died. Multivariable analysis revealed donor SNP +3142 
      (GG+CG versus CC) was associated with increased mortality (hazard ratio 1.78, 95% 
      CI 1.12-2.84; p=0.015). In contrast, five donor SNPs, -201(CC), -716(TT), 
      -56(CC), G*01:03(AA) and 14 bp INDEL, conferred reduced mortality risk. Specific 
      donor-recipient SNP pairings reduced CLAD risk. Predominantly epithelial HLA-G 
      expression was observed on TBBx without rejection. Soluble HLA-G was present in 
      higher concentrations in the BAL samples of patients who later developed 
      CLAD.Specific donor SNPs were associated with mortality risk after lung 
      transplantation, while certain donor-recipient SNP pairings modulated CLAD risk. 
      TBBx demonstrated predominantly epithelial, and therefore presumably 
      donor-derived, HLA-G expression in keeping with these observations. This study is 
      the first to demonstrate an effect of donor HLA-G SNPs on lung transplantation 
      outcome.
CI  - Copyright (c)ERS 2019.
FAU - Lazarte, Julieta
AU  - Lazarte J
AD  - Toronto Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
AD  - Cardiac Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
FAU - Ma, Jin
AU  - Ma J
AD  - University Health Network, University of Toronto, Toronto, Canada.
FAU - Martinu, Tereza
AU  - Martinu T
AD  - Toronto Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
FAU - Levy, Liran
AU  - Levy L
AD  - Toronto Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
FAU - Klement, William
AU  - Klement W
AD  - Toronto Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
FAU - White, Matthew
AU  - White M
AD  - Toronto Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
FAU - Pelling, Jacob
AU  - Pelling J
AD  - Toronto Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
FAU - Guan, Zehong
AU  - Guan Z
AD  - Toronto Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
FAU - Azad, Sassan
AU  - Azad S
AD  - Toronto Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
FAU - Tikkanen, Jussi
AU  - Tikkanen J
AD  - Toronto Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
FAU - Rao, Vivek
AU  - Rao V
AD  - Cardiac Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
FAU - Tomlinson, George
AU  - Tomlinson G
AD  - University Health Network, University of Toronto, Toronto, Canada.
FAU - Delgado, Diego
AU  - Delgado D
AD  - Cardiac Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
FAU - Keshavjee, Shaf
AU  - Keshavjee S
AD  - Toronto Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
FAU - Juvet, Stephen C
AU  - Juvet SC
AD  - Toronto Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada 
      stephen.juvet@uhn.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190815
PL  - England
TA  - Eur Respir J
JT  - The European respiratory journal
JID - 8803460
RN  - 0 (HLA-G Antigens)
RN  - 9007-49-2 (DNA)
SB  - IM
CIN - Eur Respir J. 2019 Aug 29;54(2):. PMID: 31467186
MH  - Adult
MH  - Aged
MH  - Alleles
MH  - Biopsy
MH  - DNA/genetics
MH  - Female
MH  - Genotype
MH  - Graft Survival
MH  - HLA-G Antigens/*genetics
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Leukocytes/cytology
MH  - Lung/pathology
MH  - Lung Transplantation/*mortality
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - *Polymorphism, Single Nucleotide
MH  - Proportional Hazards Models
MH  - Retrospective Studies
MH  - Risk
MH  - *Tissue Donors
COIS- Conflict of interest: J. Lazarte has nothing to disclose. Conflict of interest: 
      J. Ma has nothing to disclose. Conflict of interest: T. Martinu has nothing to 
      disclose. Conflict of interest: L. Levy has nothing to disclose. Conflict of 
      interest: W. Klement has nothing to disclose. Conflict of interest: M. White has 
      nothing to disclose. Conflict of interest: J. Pelling has nothing to disclose. 
      Conflict of interest: Z. Guan has nothing to disclose. Conflict of interest: 
      S. Azad has nothing to disclose. Conflict of interest: J. Tikkanen has nothing to 
      disclose. Conflict of interest: V. Rao reports personal fees for advisory board 
      work from Medtronic and personal fees for consultancy from Abbott, outside the 
      submitted work. Conflict of interest: G. Tomlinson has nothing to disclose. 
      Conflict of interest: D. Delgado has nothing to disclose. Conflict of interest: 
      S. Keshavjee is a founder of Perfusix Canada, a non-profit company that provides 
      ex vivo lung perfusion services to the University Health Network (Perfusix played 
      no role in the conduct of this study); and is a founder of XOR Labs, Toronto, a 
      company currently developing a medical device for ex vivo lung perfusion (not 
      used in this study). Conflict of interest: S.C. Juvet has nothing to disclose.
EDAT- 2019/06/06 06:00
MHDA- 2020/09/30 06:00
CRDT- 2019/06/06 06:00
PHST- 2018/11/07 00:00 [received]
PHST- 2019/05/12 00:00 [accepted]
PHST- 2019/06/06 06:00 [pubmed]
PHST- 2020/09/30 06:00 [medline]
PHST- 2019/06/06 06:00 [entrez]
AID - 13993003.02126-2018 [pii]
AID - 10.1183/13993003.02126-2018 [doi]
PST - epublish
SO  - Eur Respir J. 2019 Aug 15;54(2):1802126. doi: 10.1183/13993003.02126-2018. Print 
      2019 Aug.