HLA mismatching and genetically-unrelated donor
HLA mismatching refers to the degree of differences among the HLA alleles from the donor and recipient, and this concept has more clinical relevance for genetically-unrelated donation, ie non family members or deceased donors. However, what matters immunologically is the directionality of the mismatches, ie not just the nominal differences in the HLA alleles between the donor and the rcipient, but the differences in the HLA allelea of the donor that are absent in the recipient and thus able to elicit an immune response by the recipient. These differences are quantified and referred to as the number of HLA mismatches. As mentioned before, it is advantageous to have different sets of HLA alleles for a broader immune responsiveness, but in transplantation this is counterproductive as those differences or mismatches in the HLA phenotypes between donors and recipients are the main stimulator of alloresponses. It has been demonstrated that the number of HLA mismatches in clinical transplantation is associated with the risk of acute rejection and worse transplant outcomes, and organ allocation policies in many international centres give preference to donor:recipient pairs with the best possible HLA match or the minimal HLA mismatch. In fact, the negative effect of HLA mismatch appears to be more apparent in deceased donor transplantation, perhaps because the HLA mismatches become more immunogenic after the massive activation of innate system and consequent immunostimulation due to the ischaemia-reperfusion injury. It is important also to remember that the effect of HLA mismatches , allostimulating the immune system of the recipient, will persist throughout the entire life of the transplant; and this could become more relevant in organs with lower tissue quality or parenchymal reserve, characteristic of many deceased donor-derived organs, when compared to those derived from live donors.