PMID- 25003284
OWN - NLM
STAT- MEDLINE
DCOM- 20140908
LR  - 20140716
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 98
IP  - 2
DP  - 2014 Jul 27
TI  - Epitope analysis of HLA-DQ antigens: what does the antibody see?
PG  - 157-66
LID - 10.1097/TP.0000000000000220 [doi]
AB  - BACKGROUND: Human leukocyte antigen (HLA)-DQ has emerged as the alloantibody most 
      frequently associated with the generation of de novo donor-specific antibody 
      (DSA), antibody-mediated-rejection, and unfavorable transplantation outcome. 
      METHODS: The generation of HLA-DQ de novo DSA was interrogated in 40 transplant 
      recipients who were immunologically naive before their failed transplantation. 
      Eplet and epitope analyses were performed using HLAMatchmaker and Cn3D software. 
      RESULTS: Ten DQA and thirteen DQB eplets or eplet combinations were identified. 
      All but one revealed an epitope footprint that includes both the DQalpha and DQbeta 
      chains. Four examples are illustrated in detail, representing a range of 
      different epitope landscapes. A disparity between antigen density and mean 
      fluorescence intensity values for some alleles within an eplet group was noted, 
      with mean fluorescence intensity values of the lowest fluorescence bead being one 
      tenth of the highest fluorescence bead, despite the fact that the amount of 
      antigen on these beads were not significantly different. CONCLUSION: Our data 
      support the need for changing the manner in which HLA-DQ antigens and antibodies 
      are evaluated for organ transplantation. The current nomenclature system does not 
      reflect the true nature of HLA-DQ polymorphism. Moreover, epitope immunogenicity 
      likely involves more than the mere presence of a specific eplet. Because our 
      field contemplates the use of epitope matching as an approach to improve organ 
      allocation and overall outcomes, it is imperative to have accurate 
      characterization of the immunogenicity of each epitope. This will pave the way to 
      identifying acceptable mismatches and will allow risk stratification for 
      generating de novo HLA-DSA after transplantation.
FAU - Tambur, Anat R
AU  - Tambur AR
AD  - 1 Transplant Immunology Laboratory, Comprehensive Transplant Center, Feinberg 
      School of Medicine, Northwestern University, Chicago, IL. 2 Nephrology and 
      Transplantation Service, Hopital Saint-Louis, Paris, France. 3 Department of 
      Internal Medicine, Comprehensive Transplant Center, Feinberg School of Medicine, 
      Northwestern University, Chicago, IL. 4 Department of Surgery, Comprehensive 
      Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, 
      IL. 5 Address correspondence to: Anat R. Tambur, D.M.D., Ph.D., Transplant 
      Immunology Laboratory Comprehensive Transplant Center 303 E Chicago Ave, Tarry 
      Bldg suite 11-711, Chicago IL 60611.
FAU - Rosati, Jimmy
AU  - Rosati J
FAU - Roitberg, Shirley
AU  - Roitberg S
FAU - Glotz, Denis
AU  - Glotz D
FAU - Friedewald, John J
AU  - Friedewald JJ
FAU - Leventhal, Joseph R
AU  - Leventhal JR
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Epitopes)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (Isoantibodies)
SB  - IM
MH  - *Binding Sites, Antibody
MH  - *Epitope Mapping
MH  - *Epitopes
MH  - Graft Rejection/blood/*immunology
MH  - HLA-DQ Antigens/blood/chemistry/immunology
MH  - Histocompatibility
MH  - Histocompatibility Testing
MH  - Humans
MH  - Isoantibodies/blood/*immunology
MH  - Kidney Transplantation/*adverse effects
MH  - Models, Molecular
MH  - Protein Conformation
MH  - Treatment Failure
EDAT- 2014/07/09 06:00
MHDA- 2014/09/10 06:00
CRDT- 2014/07/09 06:00
PHST- 2014/07/09 06:00 [entrez]
PHST- 2014/07/09 06:00 [pubmed]
PHST- 2014/09/10 06:00 [medline]
AID - 10.1097/TP.0000000000000220 [doi]
PST - ppublish
SO  - Transplantation. 2014 Jul 27;98(2):157-66. doi: 10.1097/TP.0000000000000220.