PMID- 24744588
OWN - NLM
STAT- MEDLINE
DCOM- 20150413
LR  - 20220129
IS  - 2219-2840 (Electronic)
IS  - 1007-9327 (Print)
IS  - 1007-9327 (Linking)
VI  - 20
IP  - 14
DP  - 2014 Apr 14
TI  - HLA variants related to primary sclerosing cholangitis influence rejection after 
      liver transplantation.
PG  - 3986-4000
LID - 10.3748/wjg.v20.i14.3986 [doi]
AB  - AIM: To investigate influence of human leukocyte antigen (HLA) and killer 
      immunoglobuline-like receptor (KIR) genotypes on risks of acute rejection (AR) 
      after liver transplantation (LTX). METHODS: In this retrospective study we 
      included 143 adult donor-recipient pairs with a minimum of 6 mo follow-up after 
      LTX for whom DNA was available from both donor and recipients. Clinical data, all 
      early complications including episodes and severity of AR and graft/patient 
      survival were registered. The diagnosis of AR was based on clinical, biochemical 
      and histological criteria. All suspected episodes of AR were biopsy confirmed. 
      Key classical HLA loci (HLA-A, HLA-B, HLA-C and HLA-DRB1) were genotyped using 
      Sanger sequencing. 16 KIR genes were genotyped using a novel real time PCR 
      approach which allows for determination of the diploid copy number of each KIR 
      gene. Immunohistochemical staining for T (CD3), B (CD20) and natural killer (NK) 
      cells (CD56 and CD57) were performed on liver biopsies from 3 different patient 
      groups [primary sclerosing cholangitis (PSC), primary biliary cirrhosis and 
      non-autoimmune liver disease], 10 in each group, with similar grade of AR. 
      RESULTS: Fourty-four (31%) patients were transplanted on the basis of PSC, 40% of 
      them had AR vs 24% in the non-PSC group (P = 0.04). No significant impact of 
      donor-recipient matching for HLA and KIR genotypes was detected. In the overall 
      recipient population an increased risk of AR was detected for HLA-B*08 (P = 
      0.002, OR = 2.5; 95%CI: 1.4-4.6), HLA-C*07 (P = 0.001, OR = 2.4; 95%CI: 1.4-4.0) 
      and HLA-DRB1*03 (P = 0.03, OR = 1.9; 95%CI: 1.0-3.3) and a decreased risk for 
      HLA-DRB1*04 (P = 0.001, OR = 0.2; 95%CI: 0.1-0.5). For HLA-B*08, HLA-C*07 and 
      DRB1*04 the associations remained evident in a subgroup analysis of non-PSC 
      recipients (P = 0.04, P = 0.003 and P = 0.02, respectively). In PSC recipients 
      corresponding P values were 0.002, 0.17 and 0.01 for HLA-B*08, HLA-C*07 and 
      DRB1*04, respectively. A dosage effect of AR prevalence according to the PSC 
      associated HLA alleles was also notable in the total recipient population. For 
      HLA-B*08 the frequency of AR was 56% in HLA-B*08 homozygous recipients, 39% in 
      heterozygous recipients and 21% in recipients lacking HLA-B*08 (P = 0.02). The 
      same was observed for the HLA-C*07 allele with AR in 57%, 27% and 18% in 
      recipients being homozygous, heterozygous and lacking HLA-C*07 respectively (P = 
      0.003). Immunohistochemical analysis showed similar infiltration of T, B and NK 
      cells in biopsies with AR in all three groups. CONCLUSION: We found significant 
      associations between the PSC-associated HLA-B*08, HLA-C*07, HLA-DRB1*03 and 
      HLA-DRB1*04 alleles and risk of AR in liver transplant recipients.
FAU - Fosby, Bjarte
AU  - Fosby B
AD  - Bjarte Fosby, Sigrid Naess, Johannes R Hov, Kirsten M Boberg, Espen Melum, Tom H 
      Karlsen, Norwegian PSC Research Center, Division of Cancer, Surgery and 
      Transplantation, Oslo University Hospital, N-0424 Oslo, Norway.
FAU - Naess, Sigrid
AU  - Naess S
AD  - Bjarte Fosby, Sigrid Naess, Johannes R Hov, Kirsten M Boberg, Espen Melum, Tom H 
      Karlsen, Norwegian PSC Research Center, Division of Cancer, Surgery and 
      Transplantation, Oslo University Hospital, N-0424 Oslo, Norway.
FAU - Hov, Johannes R
AU  - Hov JR
AD  - Bjarte Fosby, Sigrid Naess, Johannes R Hov, Kirsten M Boberg, Espen Melum, Tom H 
      Karlsen, Norwegian PSC Research Center, Division of Cancer, Surgery and 
      Transplantation, Oslo University Hospital, N-0424 Oslo, Norway.
FAU - Traherne, James
AU  - Traherne J
AD  - Bjarte Fosby, Sigrid Naess, Johannes R Hov, Kirsten M Boberg, Espen Melum, Tom H 
      Karlsen, Norwegian PSC Research Center, Division of Cancer, Surgery and 
      Transplantation, Oslo University Hospital, N-0424 Oslo, Norway.
FAU - Boberg, Kirsten M
AU  - Boberg KM
AD  - Bjarte Fosby, Sigrid Naess, Johannes R Hov, Kirsten M Boberg, Espen Melum, Tom H 
      Karlsen, Norwegian PSC Research Center, Division of Cancer, Surgery and 
      Transplantation, Oslo University Hospital, N-0424 Oslo, Norway.
FAU - Trowsdale, John
AU  - Trowsdale J
AD  - Bjarte Fosby, Sigrid Naess, Johannes R Hov, Kirsten M Boberg, Espen Melum, Tom H 
      Karlsen, Norwegian PSC Research Center, Division of Cancer, Surgery and 
      Transplantation, Oslo University Hospital, N-0424 Oslo, Norway.
FAU - Foss, Aksel
AU  - Foss A
AD  - Bjarte Fosby, Sigrid Naess, Johannes R Hov, Kirsten M Boberg, Espen Melum, Tom H 
      Karlsen, Norwegian PSC Research Center, Division of Cancer, Surgery and 
      Transplantation, Oslo University Hospital, N-0424 Oslo, Norway.
FAU - Line, Pal-Dag
AU  - Line PD
AD  - Bjarte Fosby, Sigrid Naess, Johannes R Hov, Kirsten M Boberg, Espen Melum, Tom H 
      Karlsen, Norwegian PSC Research Center, Division of Cancer, Surgery and 
      Transplantation, Oslo University Hospital, N-0424 Oslo, Norway.
FAU - Franke, Andre
AU  - Franke A
AD  - Bjarte Fosby, Sigrid Naess, Johannes R Hov, Kirsten M Boberg, Espen Melum, Tom H 
      Karlsen, Norwegian PSC Research Center, Division of Cancer, Surgery and 
      Transplantation, Oslo University Hospital, N-0424 Oslo, Norway.
FAU - Melum, Espen
AU  - Melum E
AD  - Bjarte Fosby, Sigrid Naess, Johannes R Hov, Kirsten M Boberg, Espen Melum, Tom H 
      Karlsen, Norwegian PSC Research Center, Division of Cancer, Surgery and 
      Transplantation, Oslo University Hospital, N-0424 Oslo, Norway.
FAU - Scott, Helge
AU  - Scott H
AD  - Bjarte Fosby, Sigrid Naess, Johannes R Hov, Kirsten M Boberg, Espen Melum, Tom H 
      Karlsen, Norwegian PSC Research Center, Division of Cancer, Surgery and 
      Transplantation, Oslo University Hospital, N-0424 Oslo, Norway.
FAU - Karlsen, Tom H
AU  - Karlsen TH
AD  - Bjarte Fosby, Sigrid Naess, Johannes R Hov, Kirsten M Boberg, Espen Melum, Tom H 
      Karlsen, Norwegian PSC Research Center, Division of Cancer, Surgery and 
      Transplantation, Oslo University Hospital, N-0424 Oslo, Norway.
LA  - eng
GR  - 100140/Wellcome Trust/United Kingdom
GR  - G0901682/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - World J Gastroenterol
JT  - World journal of gastroenterology
JID - 100883448
RN  - 0 (HLA Antigens)
RN  - 0 (Receptors, KIR)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Alleles
MH  - Cholangitis, Sclerosing/*genetics/immunology
MH  - End Stage Liver Disease/immunology/*surgery
MH  - Female
MH  - Genotype
MH  - *Graft Rejection
MH  - Graft Survival
MH  - HLA Antigens/*genetics/immunology
MH  - Humans
MH  - Immunohistochemistry
MH  - *Liver Transplantation
MH  - Male
MH  - Middle Aged
MH  - Receptors, KIR/genetics
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC3983454
OTO - NOTNLM
OT  - Acute rejection
OT  - Human leukocyte antigen
OT  - Killer immunoglobulin-like receptor
OT  - Liver transplantation
OT  - Primary sclerosing cholangitis
EDAT- 2014/04/20 06:00
MHDA- 2015/04/14 06:00
PMCR- 2014/04/14
CRDT- 2014/04/19 06:00
PHST- 2014/01/30 00:00 [received]
PHST- 2014/02/11 00:00 [revised]
PHST- 2014/03/07 00:00 [accepted]
PHST- 2014/04/19 06:00 [entrez]
PHST- 2014/04/20 06:00 [pubmed]
PHST- 2015/04/14 06:00 [medline]
PHST- 2014/04/14 00:00 [pmc-release]
AID - 10.3748/wjg.v20.i14.3986 [doi]
PST - ppublish
SO  - World J Gastroenterol. 2014 Apr 14;20(14):3986-4000. doi: 
      10.3748/wjg.v20.i14.3986.