Claas F. H. J.

Department of Immunohematology & Blood Bank, University Medical Center, Leiden

Background: In bone marrow and kidney transplantation, HLA matching is routinely used as an important allocation parameter. HLA matching of donor and recipient has also shown to improve graft survival in corneal transplantation, especially in high risk cases. The selection of well-matched donors is hampered by the enormous polymorphism of the HLA system. This was already the case when HLA typing was routinely performed by serological techniques, but the introduction of molecular typing techniques has led to an almost exponential increase of the number of HLA alleles. In this perspective, it is not realistic to aim at the selection of a completely HLA matched donor for every patient. Most of the patients can only be transplanted with a partly HLA mismatched donor. By retrospective analysis of graft survival data, it became clear that not every HLA mismatch has the same detrimental effect on graft survival. Some HLA mismatches appear to be more immunogenic than other ones. These retrospective studies, supported by in vitro data on CTL induction, have led to definition of permissible and taboo mismatches. Grafts with permissible mismatches have a similar survival as completely HLA matched grafts, whereas taboo mismatches lead to a significantly poorer graft survival than other mismatches. Until recently, studies focussing on the relative immunogenicity of HLA mismatches were dependent on extensive analyses of graft survival data and labour intensive laboratory testing.
Methods: However, a special computer program developed by R. Duquesnoy (Pittsburgh, USA) may be useful in this respect. This program calculates for a particular HLA mismatch how many polymorphic sites (antibody epitopes) are available to be recognized as foreign by the immune system of the patient. It is indeed possible that one mismatched HLA antigen differs at more than 10 polymorphic sites from the HLA molecules of the patient, whereas another HLA mismatch has no or only 1 polymorphic site different from the patient. It is to be expected that the second mismatch is less immunogenic compared to the first one.
Results: Studies are in progress to validate the use of this computer program for the prediction of a humoral or cellular alloimmune response leading to graft rejection.
Conclusion: These studies should reveal whether this approach can be used in the future for the identification of permissible versus taboo mismatches and the selection of the best, although partly HLA mismatched, donor for a particular patient.

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