PMID- 30955869
OWN - NLM
STAT- MEDLINE
DCOM- 20200921
LR  - 20200921
IS  - 1523-1755 (Electronic)
IS  - 0085-2538 (Linking)
VI  - 95
IP  - 6
DP  - 2019 Jun
TI  - Epitope load identifies kidney transplant recipients at risk of allosensitization 
      following minimization of immunosuppression.
PG  - 1471-1485
LID - S0085-2538(19)30115-2 [pii]
LID - 10.1016/j.kint.2018.12.029 [doi]
AB  - Human leukocyte antigen (HLA) mismatching and minimization of immunosuppression 
      are two major risk factors for the development of de novo donor-specific 
      antibodies, which are associated with reduced kidney graft survival. Antibodies 
      do not recognize whole HLA antigens but rather individual epitopes, which are 
      short sequences of amino acids in accessible positions. However, compatibility is 
      still assessed by the simple count of mismatched HLA antigens. We hypothesized 
      that the number of mismatched epitopes, or ("epitope load") would identify 
      patients at the highest risk of developing donor specific antibodies following 
      minimization of immunosuppression. We determined epitope load in 89 clinical 
      trial participants who converted from cyclosporine to everolimus 3 months after 
      kidney transplantation. Twenty-nine participants (32.6%) developed de novo donor 
      specific antibodies. Compared to the number of HLA mismatches, epitope load was 
      more strongly associated with the development of donor specific antibodies. 
      Participants with an epitope load greater than 27 had a 12-fold relative risk of 
      developing donor-specific antibodies compared to those with an epitope load below 
      that threshold. Using that threshold, epitope load would have missed only one 
      participant who subsequently developed donor specific antibodies, compared to 8 
      missed cases based on a 6-antigen mismatch. DQ7 was the most frequent antigenic 
      target of donor specific antibodies in our population, and some DQ7 epitopes 
      appeared to be more frequently involved than others. Assessing epitope load 
      before minimizing immunosuppression may be a more efficient tool to identify 
      patients at the highest risk of allosensitization.
CI  - Copyright (c) 2019 International Society of Nephrology. Published by Elsevier Inc. 
      All rights reserved.
FAU - Snanoudj, Renaud
AU  - Snanoudj R
AD  - Service de Nephrologie, Hemodialyse et Transplantation Renale, Hopital Foch, 
      Suresnes, France; CESP, INSERM, Universite Paris-Sud, UVSQ, Universite 
      Paris-Saclay, Villejuif, France. Electronic address: r.snanoudj@hopital-foch.com.
FAU - Kamar, Nassim
AU  - Kamar N
AD  - Service de Nephrologie et Transplantation d'organe, CHU Rangueil, Toulouse, 
      France.
FAU - Cassuto, Elisabeth
AU  - Cassuto E
AD  - Service de Nephrologie, Hopital Pasteur, CHU de Nice, Nice, France.
FAU - Caillard, Sophie
AU  - Caillard S
AD  - Service de Nephrologie et Transplantation, CHU de Strasbourg, Strasbourg, France.
FAU - Metzger, Marie
AU  - Metzger M
AD  - CESP, INSERM, Universite Paris-Sud, UVSQ, Universite Paris-Saclay, Villejuif, 
      France.
FAU - Merville, Pierre
AU  - Merville P
AD  - Service de Nephrologie et Transplantation, Hopital Pellegrin, Bordeaux, France.
FAU - Thierry, Antoine
AU  - Thierry A
AD  - Service de Nephrologie et Transplantation, CHU de Poitiers, Poitiers, France.
FAU - Jollet, Isabelle
AU  - Jollet I
AD  - Laboratoire HLA, EFS de Poitiers, Poitiers, France.
FAU - Grimbert, Philippe
AU  - Grimbert P
AD  - Service de Nephrologie et Transplantation, Hopital Henri Mondor, Creteil, France.
FAU - Anglicheau, Dany
AU  - Anglicheau D
AD  - Service de Transplantation et Nephrologie, Hopital Necker, Assistance Publique 
      Hopitaux de Paris, Paris, France.
FAU - Hazzan, Marc
AU  - Hazzan M
AD  - Service de Nephrologie, Hopital Claude Huriez, CHRU de Lille, Lille, France.
FAU - Choukroun, Gabriel
AU  - Choukroun G
AD  - Service de Nephrologie, CHU Amiens-Picardie, Amiens, France.
FAU - Hurault De Ligny, Bruno
AU  - Hurault De Ligny B
AD  - Service de Nephrologie et Transplantation, CHU de Caen, Caen, France.
FAU - Janbon, Benedicte
AU  - Janbon B
AD  - Service de Nephrologie et Transplantation, CHU de Grenoble, Grenoble, France.
FAU - Vuiblet, Vincent
AU  - Vuiblet V
AD  - Service de Nephrologie, Hopital Maison Blanche, Reims, France.
FAU - Devys, Anne
AU  - Devys A
AD  - Etablissement francais du sang - Centre Pays de Loire, Angers, France.
FAU - Le Meur, Yann
AU  - Le Meur Y
AD  - Service de Nephrologie, CHU de Brest, Brest, France.
FAU - Delahousse, Michel
AU  - Delahousse M
AD  - Service de Nephrologie, Hemodialyse et Transplantation Renale, Hopital Foch, 
      Suresnes, France.
FAU - Morelon, Emmanuel
AU  - Morelon E
AD  - Service de Transplantation, Nephrologie et Immunologie Clinique, Hopital Edouard 
      Herriot, Hospices Civils de Lyon, Lyon, France.
FAU - Bailly, Elodie
AU  - Bailly E
AD  - Service de Nephrologie, Hopital Bretonneau, CHU de Tours, Tours, France.
FAU - Girerd, Sophie
AU  - Girerd S
AD  - Service de Nephrologie, CHU Nancy Brabois, Nancy, France.
FAU - Amokrane, Kahina
AU  - Amokrane K
AD  - Laboratoire d'Immunologie et Histocompatibilite Hopital Saint-Louis, Paris, 
      France; INSERM UMRs 1160, Institut Universitaire d'Hematologie, Universite Paris 
      Diderot, Paris, France.
FAU - Legendre, Christophe
AU  - Legendre C
AD  - Service de Transplantation et Nephrologie, Hopital Necker, Assistance Publique 
      Hopitaux de Paris, Paris, France.
FAU - Hertig, Alexandre
AU  - Hertig A
AD  - Service de Nephrologie et Transplantation, Hopital Tenon, Paris, France.
FAU - Rondeau, Eric
AU  - Rondeau E
AD  - Service de Nephrologie et Transplantation, Hopital Tenon, Paris, France.
FAU - Taupin, Jean-Luc
AU  - Taupin JL
AD  - Laboratoire d'Immunologie et Histocompatibilite Hopital Saint-Louis, Paris, 
      France; INSERM UMRs 1160, Institut Universitaire d'Hematologie, Universite Paris 
      Diderot, Paris, France.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20190305
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Epitopes)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ7 antigen)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Isoantigens)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - 9HW64Q8G6G (Everolimus)
SB  - IM
MH  - Adult
MH  - Cyclosporine/administration & dosage/adverse effects
MH  - Drug Substitution
MH  - Epitopes/immunology
MH  - Everolimus/administration & dosage/adverse effects
MH  - Female
MH  - Follow-Up Studies
MH  - Graft Rejection/blood/immunology/*prevention & control
MH  - Graft Survival/immunology
MH  - HLA-DQ Antigens/*blood/immunology
MH  - Histocompatibility Testing
MH  - Humans
MH  - Immunosuppressive Agents/*administration & dosage/adverse effects
MH  - Isoantigens/*blood/immunology
MH  - Kidney Transplantation/*adverse effects
MH  - Male
MH  - Middle Aged
MH  - *Patient Selection
MH  - Transplantation, Homologous/adverse effects
OTO - NOTNLM
OT  - HLA mismatching
OT  - acute rejection
OT  - antibody-mediated rejection
OT  - epitopes
OT  - immunosuppression minimization
OT  - kidney transplantation
EDAT- 2019/04/09 06:00
MHDA- 2020/09/22 06:00
CRDT- 2019/04/09 06:00
PHST- 2018/03/18 00:00 [received]
PHST- 2018/12/07 00:00 [revised]
PHST- 2018/12/28 00:00 [accepted]
PHST- 2019/04/09 06:00 [pubmed]
PHST- 2020/09/22 06:00 [medline]
PHST- 2019/04/09 06:00 [entrez]
AID - S0085-2538(19)30115-2 [pii]
AID - 10.1016/j.kint.2018.12.029 [doi]
PST - ppublish
SO  - Kidney Int. 2019 Jun;95(6):1471-1485. doi: 10.1016/j.kint.2018.12.029. Epub 2019 
      Mar 5.