HLA class I amino acid sequence-based matching after interlocus subtraction and long-term outcome after deceased donor kidney transplantation.
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.