HLA system in solid organ transplantation part 23

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.