The number of amino acid triplet differences between patient and donor is predictive for the antibody reactivity against mismatched human leukocyte antigens

Background. The correlation between antibody production against mismatched donor human leukocyte antigens (HLA) and the number of amino acid sequence mismatches was analyzed in patients who rejected a kidney transplant (n=146). Methods. A similar analysis was performed for the antibody production of women against the paternal HLA antigens of their child (n = 1,397). The amino acid sequence (triplet) differences were analyzed using the HLAMatchmaker algorithm. Results. In both groups, a positive correlation was found between the number of triplet mismatches and the percentage of individuals producing antibodies (P<0.0001). If zero triplet mismatches were present, no antibodies were formed in all cases. When 11 or 12 triplet mismatches were present, 94% of the transplant patients produced antibodies against the donor. In pregnancy, 11 or 12 triplet mismatches led to 27% of the women producing specific antibodies. Conclusions. These results indicate that the immunogenicity of the fetus is lower than that of a rejected kidney and that analysis of the number of triplet mismatches can predict the antibody reactivity against the mismatched HLA antigens.