PMID- 19920778
OWN - NLM
STAT- MEDLINE
DCOM- 20091203
LR  - 20211028
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 88
IP  - 6
DP  - 2009 Sep 27
TI  - Predicting HLA class I alloantigen immunogenicity from the number and 
      physiochemical properties of amino acid polymorphisms.
PG  - 791-8
LID - 10.1097/TP.0b013e3181b4a9ff [doi]
AB  - BACKGROUND: Knowledge of the human leukocyte antigen (HLA) amino acid (AA) 
      sequence combined with crystallographic structural data may enable prediction of 
      the relative immunogenicity of individual donor/recipient HLA mismatches. 
      METHODS: Multiple sera from 32 highly sensitized patients awaiting kidney 
      transplantation were screened using Luminex/single-antigen beads to determine the 
      HLA-specific antibody levels against mismatched HLA class I specificities. A 
      computer program was developed to allow intralocus and interlocus comparison of 
      mismatched HLA-A and -B specificities with corresponding recipient HLA class I 
      type, and to determine the number, position, and physiochemical disparity 
      (hydrophobicity and electrostatic charge) of polymorphic AA. RESULTS: 
      HLA-specific antibody was detected against 1666 (85%) of the 1964 mismatched HLA 
      specificities evaluated, with a close correlation between increasing number of AA 
      polymorphisms and the presence and magnitude of the alloantibody response 
      (P<0.0001). Hydrophobicity and electrostatic charge disparity scores were 
      independent predictors of alloantibody production (adjusted P=0.0009 and 
      P=0.0005, respectively). Mismatched specificities with physiochemical scores 
      within the first decile of the scale led to weak alloantibody responses (median 
      fluorescence intensity 2330), whereas those with scores above the sixth decile 
      led to strong alloantibody production (median fluorescence intensity >10,000). 
      CONCLUSION: Differences in AA number, hydrophobicity, and electrostatic charge 
      between HLA class I specificities enable prediction of donor HLA class I types 
      with low immunogenicity for a given recipient.
FAU - Kosmoliaptsis, Vasilis
AU  - Kosmoliaptsis V
AD  - Tissue Typing Laboratory, Cambridge University Hospitals NHS Foundation Trust, 
      Addenbrooke's Hospital, Cambridge, England.
FAU - Chaudhry, Afzal N
AU  - Chaudhry AN
FAU - Sharples, Linda D
AU  - Sharples LD
FAU - Halsall, David J
AU  - Halsall DJ
FAU - Dafforn, Timothy R
AU  - Dafforn TR
FAU - Bradley, J Andrew
AU  - Bradley JA
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 (HLA Antigens)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-C Antigens)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Isoantibodies)
SB  - IM
CIN - Transplantation. 2009 Sep 27;88(6):760-1. PMID: 19920773
MH  - Adult
MH  - Aged
MH  - Amino Acids/chemistry/genetics
MH  - Female
MH  - HLA Antigens/*chemistry/classification/*genetics
MH  - HLA-A Antigens/chemistry/genetics
MH  - HLA-B Antigens/chemistry/genetics
MH  - HLA-C Antigens/chemistry/genetics
MH  - Histocompatibility Testing/statistics & numerical data
MH  - Humans
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Immunochemistry
MH  - Immunoglobulin G/blood
MH  - Isoantibodies/blood
MH  - Kidney Transplantation/immunology
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Genetic
MH  - Software
MH  - Static Electricity
MH  - Tissue Donors
MH  - Transplantation Immunology
EDAT- 2009/11/19 06:00
MHDA- 2009/12/16 06:00
CRDT- 2009/11/19 06:00
PHST- 2009/11/19 06:00 [entrez]
PHST- 2009/11/19 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - 00007890-200909270-00009 [pii]
AID - 10.1097/TP.0b013e3181b4a9ff [doi]
PST - ppublish
SO  - Transplantation. 2009 Sep 27;88(6):791-8. doi: 10.1097/TP.0b013e3181b4a9ff.