Predicting HLA Class I Alloantigen Immunogenicity From the Number and Physiochemical Properties of Amino Acid Polymorphisms

• DOI: 10.1097/tp.0b013e3181b4a9ff
• Publication Date: 2009-09-18T12:20:31Z
• Authors: Vasilis Kosmoliap...; Afzal N. Chaudhry; Linda D. Sharples; David J. Halsall; Timothy R. Dafforn; J Andrew Bradley; Craig J. Taylor
• Keywords: Alloimmunity; Immunogenetics

Knowledge of the human leukocyte antigen (HLA) amino acid (AA) sequence combined with crystallographic structural data may enable prediction relative immunogenicity individual donor/recipient HLA mismatches.Multiple sera from 32 highly sensitized patients awaiting kidney transplantation were screened using Luminex/single-antigen beads to determine HLA-specific antibody levels against mismatched class I specificities. A computer program was developed allow intralocus and interlocus comparison HLA-A -B specificities corresponding recipient type, number, position, physiochemical disparity (hydrophobicity electrostatic charge) polymorphic AA.HLA-specific detected 1666 (85%) 1964 evaluated, a close correlation between increasing number AA polymorphisms presence magnitude alloantibody response (P<0.0001). Hydrophobicity charge scores independent predictors production (adjusted P=0.0009 P=0.0005, respectively). Mismatched within first decile scale led weak responses (median fluorescence intensity 2330), whereas those above sixth strong >10,000).Differences in hydrophobicity, donor types low for given recipient.