PMID- 30142248
OWN - NLM
STAT- MEDLINE
DCOM- 20190606
LR  - 20211031
IS  - 1527-6473 (Electronic)
IS  - 1527-6465 (Linking)
VI  - 24
IP  - 8
DP  - 2018 Aug
TI  - Class II Human Leukocyte Antigen Epitope Mismatch Predicts De Novo Donor-Specific 
      Antibody Formation After Liver Transplantation.
PG  - 1101-1108
LID - 10.1002/lt.25286 [doi]
AB  - Formation of de novo donor-specific antibodies (dn-DSAs) has been associated with 
      longterm immunologic complications after liver transplantation (LT). We 
      hypothesized that human leukocyte antigen (HLA) epitope/eplet mismatch (MM) is a 
      marker of immunogenicity and a risk factor for dn-DSA formation. Sera from 80 LT 
      recipients were prospectively screened for dn-DSA by a Luminex single-antigen 
      test (One Lambda, Inc., Canoga Park, CA) at 1, 2, 3, 6, 12, 18, 24, and 36 months 
      after LT. HLA typing of the recipients and donors was performed using polymerase 
      chain reaction (PCR)-SSP and PCR-SSOP Luminex low-resolution methods (One Lambda, 
      Inc.). The HLAMatchmaker computer algorithm was used for identification of MM 
      eplets at HLA-DRB1 and -DQA1/B1 loci. Luminex single-antigen bead solid phase 
      assay was used for antibody analysis. Standard immunosuppression included 
      thymoglobulin-rituximab induction and tacrolimus maintenance. There were 27 (34%) 
      patients who developed dn-DSA. There were no episodes of antibody-mediated 
      rejection, and 9 (11%) developed acute cellular rejection (ACR). A positive 
      crossmatch status and a higher number of HLA-A, -B, -DR, and -ABDR MMs were not 
      associated with dn-DSA formation. Patients developing dn-DSA had a significantly 
      higher number of total (38 +/- 2.7 versus 28 +/- 2.3; P = 0.01) and antibody-verified 
      (AbVer; 14 +/- 1.1 versus 10 +/- 1; P = 0.015) class II MM eplets. By a multivariate 
      regression analysis, the number of class II MM eplets was strongly associated 
      with risk of class II dn-DSA formation (odds ratio [OR], 1.2; P < 0.01). Patients 
      with ACR had a significantly higher number of total (20.2 +/- 1.3 versus 13.9 +/- 
      0.9; P < 0.01) as well as AbVer (10.7 +/- 1.1 versus 7.5 +/- 0.6; P = 0.03) class I 
      MM eplets. In conclusion, donor-recipient HLA epitope MM is associated with a 
      risk of dn-DSA formation and rejection after LT. However, further studies are 
      required to evaluate the clinical utility of epitope matching in LT.
CI  - (c) 2018 The Authors. Liver Transplantation published by Wiley Periodicals, Inc. on 
      behalf of American Association for the Study of Liver Diseases.
FAU - Kubal, Chandrashekhar A
AU  - Kubal CA
AUID- ORCID: 0000-0003-4043-2943
AD  - Transplant Division, Department of Surgery, Indiana University School of 
      Medicine, Indianapolis, IN.
FAU - Mangus, Richard
AU  - Mangus R
AD  - Transplant Division, Department of Surgery, Indiana University School of 
      Medicine, Indianapolis, IN.
FAU - Ekser, Burcin
AU  - Ekser B
AD  - Transplant Division, Department of Surgery, Indiana University School of 
      Medicine, Indianapolis, IN.
FAU - Mihaylov, Plamen
AU  - Mihaylov P
AD  - Transplant Division, Department of Surgery, Indiana University School of 
      Medicine, Indianapolis, IN.
FAU - Ceballos, Brian
AU  - Ceballos B
AD  - Transplant Division, Department of Surgery, Indiana University School of 
      Medicine, Indianapolis, IN.
FAU - Higgins, Nancy
AU  - Higgins N
AD  - Indiana University Health Inc., Methodist Hospital, Histocompatibility 
      Laboratory, Indianapolis, IN.
FAU - Chalasani, Naga
AU  - Chalasani N
AD  - Division of Gastroenterology and Hepatology, Department of Medicine, Indiana 
      University School of Medicine, Indianapolis, IN.
FAU - Ghabril, Marwan
AU  - Ghabril M
AD  - Division of Gastroenterology and Hepatology, Department of Medicine, Indiana 
      University School of Medicine, Indianapolis, IN.
FAU - Nephew, Lauren
AU  - Nephew L
AD  - Division of Gastroenterology and Hepatology, Department of Medicine, Indiana 
      University School of Medicine, Indianapolis, IN.
FAU - Lobashevsky, Andrew
AU  - Lobashevsky A
AD  - Indiana University Health Inc., Methodist Hospital, Histocompatibility 
      Laboratory, Indianapolis, IN.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Liver Transpl
JT  - Liver transplantation : official publication of the American Association for the 
      Study of Liver Diseases and the International Liver Transplantation Society
JID - 100909185
RN  - 0 (Epitopes)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Isoantibodies)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
CIN - Liver Transpl. 2019 Jan;25(1):184-185. PMID: 30329206
CIN - Liver Transpl. 2021 Nov;27(11):1592-1602. PMID: 34310028
MH  - Adult
MH  - Aged
MH  - End Stage Liver Disease/surgery
MH  - Epitopes/immunology
MH  - Female
MH  - Graft Rejection/blood/*diagnosis/immunology/prevention & control
MH  - Graft Survival
MH  - Histocompatibility Antigens Class II/*immunology
MH  - *Histocompatibility Testing
MH  - Humans
MH  - Immunosuppressive Agents/therapeutic use
MH  - Isoantibodies/*blood/immunology/isolation & purification
MH  - Liver Transplantation/*adverse effects
MH  - Male
MH  - Middle Aged
MH  - Predictive Value of Tests
MH  - Prognosis
MH  - Prospective Studies
MH  - Tacrolimus/therapeutic use
MH  - Tissue Donors
EDAT- 2018/08/25 06:00
MHDA- 2019/06/07 06:00
CRDT- 2018/08/25 06:00
PHST- 2018/02/09 00:00 [received]
PHST- 2018/05/23 00:00 [revised]
PHST- 2018/05/23 00:00 [accepted]
PHST- 2018/08/25 06:00 [entrez]
PHST- 2018/08/25 06:00 [pubmed]
PHST- 2019/06/07 06:00 [medline]
AID - 10.1002/lt.25286 [doi]
PST - ppublish
SO  - Liver Transpl. 2018 Aug;24(8):1101-1108. doi: 10.1002/lt.25286.