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.