PMID- 18580476
OWN - NLM
STAT- MEDLINE
DCOM- 20080813
LR  - 20211028
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 85
IP  - 12
DP  - 2008 Jun 27
TI  - Predicting the immunogenicity of human leukocyte antigen class I alloantigens 
      using structural epitope analysis determined by HLAMatchmaker.
PG  - 1817-25
LID - 10.1097/TP.0b013e31817441d6 [doi]
AB  - BACKGROUND: Human leukocyte antigen (HLA) matching strategies for kidney 
      transplantation assign equal weighting to mismatches at a particular locus and 
      take no account of variation in immunogenicity according to recipient HLA type. 
      We examined the ability of intra- and interlocus analysis of amino-acid 
      polymorphisms at continuous (triplet) and discontinuous positions (eplet) defined 
      by the HLAMatchmaker program to predict alloantigen immunogenicity. METHODS: Sera 
      from highly sensitized patients were screened for HLA class-I alloantibodies and 
      mismatched combinations were analyzed using HLAMatchmaker to determine the number 
      of triplet or extended-triplet and eplet mismatches. RESULTS: Logistic regression 
      analysis revealed a strong correlation between the number of triplet or 
      extended-triplet and eplet mismatches and both the presence and magnitude of 
      alloantibody to mismatched HLA-A and -B specificities. The additional structural 
      information provided by eplet analysis gave increased discrimination of 
      mismatched-HLA specificities for alloantigens with greatest sequence disparity 
      but this did not further improve the ability of triplet analysis to predict 
      alloantigen immunogenicity. High antibody levels were observed for several 
      mismatched-HLA combinations with zero triplet or eplet mismatches indicating that 
      self triplets or eplets expressed in different conformations do not always 
      predict nonimmunogenic epitopes. CONCLUSION: Analysis of recipient HLA type and 
      mismatched-HLA alloantigens using the HLAMatchmaker algorithm allows prediction 
      of immunogenic donor HLA types.
FAU - Kosmoliaptsis, Vasilis
AU  - Kosmoliaptsis V
AD  - Tissue Typing Laboratory, Cambridge University Hospitals NHS Foundation Trust, 
      Addenbrooke's Hospital, Cambridge, United Kingdom.
FAU - Bradley, J Andrew
AU  - Bradley JA
FAU - Sharples, Linda D
AU  - Sharples LD
FAU - Chaudhry, Afzal
AU  - Chaudhry A
FAU - Key, Timothy
AU  - Key T
FAU - Goodman, Reyna S
AU  - Goodman RS
FAU - Taylor, Craig J
AU  - Taylor CJ
LA  - eng
GR  - MC_U105232027/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Amino Acids)
RN  - 0 (Antibodies)
RN  - 0 (Epitopes)
RN  - 0 (Isoantigens)
SB  - IM
MH  - Adult
MH  - *Algorithms
MH  - Amino Acids/immunology
MH  - Antibodies/immunology
MH  - Epitopes/*genetics/immunology
MH  - Female
MH  - Genes, MHC Class I/*genetics/*immunology
MH  - Graft Rejection/immunology/prevention & control
MH  - Humans
MH  - *Immunogenetics
MH  - Isoantigens/*genetics/immunology
MH  - Kidney Transplantation/immunology
MH  - Logistic Models
MH  - Male
MH  - Middle Aged
MH  - Predictive Value of Tests
EDAT- 2008/06/27 09:00
MHDA- 2008/08/14 09:00
CRDT- 2008/06/27 09:00
PHST- 2008/06/27 09:00 [pubmed]
PHST- 2008/08/14 09:00 [medline]
PHST- 2008/06/27 09:00 [entrez]
AID - 00007890-200806270-00021 [pii]
AID - 10.1097/TP.0b013e31817441d6 [doi]
PST - ppublish
SO  - Transplantation. 2008 Jun 27;85(12):1817-25. doi: 10.1097/TP.0b013e31817441d6.