PMID- 21079553
OWN - NLM
STAT- MEDLINE
DCOM- 20110223
LR  - 20211020
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 91
IP  - 2
DP  - 2011 Jan 27
TI  - Predicting HLA class II alloantigen immunogenicity from the number and 
      physiochemical properties of amino acid polymorphisms.
PG  - 183-90
LID - 10.1097/TP.0b013e3181ffff99 [doi]
AB  - BACKGROUND: We have shown previously that human leukocyte antigen (HLA) class I 
      immunogenicity can be predicted by the number, position, and physiochemical 
      differences of polymorphic amino acids (AAs). We have now modeled the structural 
      and physiochemical polymorphisms of HLA class II alloantigens and correlated 
      these with humoral alloimmunity in sensitized patients awaiting kidney 
      transplantation. METHODS: Sera obtained from 30 patients with high levels of IgG 
      HLA-specific antibodies were screened using single-antigen HLA antibody detection 
      beads. A computer program was developed to determine the number of AA mismatches 
      (after interlocus and intralocus subtraction) and their hydrophobicity and 
      electrostatic mismatch score for each mismatched HLA-DR and -DQ specificity. 
      Regression methods were used to compare these variables with the occurrence and 
      magnitude of alloantibody responses. RESULTS: HLA-specific antibody was detected 
      against 879 (55%) of 1604 mismatched HLA specificities evaluated. There was a 
      strong correlation between increasing number of AA mismatches and the occurrence 
      (P<0.001, odds ratio 3.85 per AA) and magnitude of alloantibody responses 
      (P<0.001); only 6% of alloantigens with 0 to 2 mismatched AA-induced alloantibody 
      (median fluorescence intensity 37) compared with 82% of alloantigens with more 
      than or equal to 20 mismatched AAs (median fluorescence intensity 9969). 
      Hydrophobicity and electrostatic mismatch scores also correlated closely with 
      alloantibody response (P<0.001), but neither variable had independent predictive 
      value over the number of AA mismatches alone. CONCLUSION: Differences in the 
      number of polymorphic AA mismatches and their physiochemical properties for a 
      given recipient HLA type are strong predictors of class II alloantigen 
      immunogenicity and alloantibody response before kidney transplantation.
FAU - Kosmoliaptsis, Vasilis
AU  - Kosmoliaptsis V
AD  - Tissue Typing Laboratory, Cambridge University Hospitals NHS Foundation Trust, 
      Addenbrooke's Hospital, Cambridge, England. kosmo@doctors.org.uk
FAU - Sharples, Linda D
AU  - Sharples LD
FAU - Chaudhry, Afzal N
AU  - Chaudhry AN
FAU - Halsall, David J
AU  - Halsall DJ
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 (HLA-D Antigens)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Isoantibodies)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Amino Acid Sequence
MH  - Chemical Phenomena
MH  - Female
MH  - HLA-D Antigens/*chemistry/*genetics/immunology
MH  - HLA-DQ Antigens/chemistry/genetics/immunology
MH  - HLA-DR Antigens/chemistry/genetics/immunology
MH  - Humans
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Isoantibodies/blood
MH  - Kidney Transplantation/immunology
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Genetic
MH  - Static Electricity
MH  - Young Adult
EDAT- 2010/11/17 06:00
MHDA- 2011/02/24 06:00
CRDT- 2010/11/17 06:00
PHST- 2010/11/17 06:00 [entrez]
PHST- 2010/11/17 06:00 [pubmed]
PHST- 2011/02/24 06:00 [medline]
AID - 10.1097/TP.0b013e3181ffff99 [doi]
PST - ppublish
SO  - Transplantation. 2011 Jan 27;91(2):183-90. doi: 10.1097/TP.0b013e3181ffff99.