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We have shown previously that human leukocyte antigen (HLA) immunogenicity, defined by the physiochemical properties of mismatched amino acids, predicts humoral alloimmunity, and now report the effect on long-term graft survival after kidney transplantation. The influence of HLA-A and -B mismatch, number of amino acid mismatches (after interlocus subtraction) and their physiochemical (electrostatic and hydrophobic) disparity on the outcome of fully HLA matched and single HLA-A or -B mismatched deceased donor kidney transplants undertaken in the United Kingdom (1990-2005) were analyzed (n = 5,247). Grafts with a single HLA-A or -B mismatch had significantly lower survival than fully matched transplants (81.9% vs 84.2% at 5 years, p = 0.004). However, single HLA-A or -B mismatched grafts with no or one amino acid mismatch had better survival than grafts with two or more amino acid mismatches (89.3% vs 81.8% at 5 years, HR 1.5, p = 0.03). The number of mismatched amino acids was an independent predictor of transplant survival after adjusting for the underlying HLA matching effect (p = 0.02). Physiochemical disparity scores correlated closely with amino acid mismatches and provided no additional predictive value. The immunogenicity of HLA class I alloantigens defined at the level of amino acid sequence correlates more closely with outcome after renal transplantation than conventional serologic HLA matching.

Original publication

DOI

10.1016/j.humimm.2010.06.003

Type

Journal article

Journal

Hum Immunol

Publication Date

09/2010

Volume

71

Pages

851 - 856

Keywords

Adolescent, Adult, Aged, Aged, 80 and over, Amino Acid Sequence, Amino Acid Substitution, Amino Acids, Child, Child, Preschool, Graft Survival, HLA-A Antigens, HLA-B Antigens, HLA-DR Antigens, Histocompatibility Antigens Class I, Histocompatibility Testing, Humans, Hydrophobic and Hydrophilic Interactions, Infant, Kidney Transplantation, Middle Aged, Proportional Hazards Models, Static Electricity, Tissue Donors, United Kingdom, Young Adult