THE NUMBER OF AMINO ACID SEQUENCE DIFFERENCES BETWEEN PATIENT AND DONOR IS PREDICTIVE FOR THE ANTIBODY RESPONSE AGAINST THE MISMATCHED HLA ANTIGENS.

3.1
#23-OR
THE NUMBER OF AMINO ACID SEQUENCE DIFFERENCES BETWEEN PATIENT AND DONOR IS PREDICTIVE FOR THE ANTIBODY RESPONSE AGAINST THE MISMATCHED HLA ANTIGENS.
Marlies K.A. Dankers , Marian Witvliet , Dave L. Roelen , Peter de Lange , Nelleke Korfage , Guido G. Persijn , Ilias I.N. Doxiadis and Frans H.J. Claas . Leiden Netherlands, LUMC, Immunohematology and Blood Transfusion and Leiden Netherlands, Eurotransplant Foundation .

The immunogenicity of an HLA mismatch depends on the HLA phenotype of the donor as well as that of the recipient. This differential immunogenicity might be explained by specific amino acid sequence differences between donor and recipient.
We analysed whether in patients who rejected a kidney transplant (N=146) a correlation exists between the antibody production against the donor and the number of triplet mismatches. A similar approach was used for the antibody production of women against the mismatched paternal HLA antigens of the child (N=1397). The aminoacid sequence differences were analysed by HLAMatchmaker, which defines the mismatches by triplets of aminoacid residues on antibody accessible sites of HLA molecules.The results show that a strong positive correlation can be 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 11-12 triplet mismastches were present, 94% of the transplanted patients produced specific antibodies. In pregnancy, the same number of triplet mismatches leads to only 27% of the women producing specific antibodies. The contribution of the placenta, which acts as a filter for the passage of antibodies to the fetus may be responsible for this difference.
The results indicate that the number of triplet mismatches between patient and donor can predict the antibody reactivity and implementation of this information in a kidney allocation scheme might reduce the incidence of humoral graft rejection and minimize the sensitization grade of retransplant candidates.