Our reported
post-operative transfusion rate of 43% is very similar to those reported elsewhere [28] and [29]. The reason Selleckchem ZVADFMK for the higher rate of peri-operative transfusion in patients with DSA compared with Non-DSA is therefore uncertain. It may be due to the greater medical and surgical complexities of this patient group and their greater waiting time on dialysis for example. However, it is notable that there was no difference in gender, re-transplantation, deceased donors or Pre-RBCT between the DSA and Non-DSA groups at time of surgery, or between the haemoglobin at surgery or at 1 month post-surgery. Although residual confounding by indication remains possible, it is not possible to either entirely adjust or explain and this difference requires further testing. The immunological interaction of blood transfusion and transplantation is complex. Pre-RBCT is associated with better graft outcomes and less acute rejection, and this is suggested to be due to immunomodulation with down-regulation of an immune response and the induction of regulatory T-cells [11] and [30]. Indeed
our study confirms the continued benefit of Pre-RBCT alone with this group having the lowest rate of Non-AMR. We also confirm that Pre-RBCT is still associated with an increased risk of HLA-antibody sensitisation. Several recent reports [28] and [29] raise some concern that post-operative transfusion is associated with poor graft outcome. However these studies did not consider sensitisation or prior transfusion Staurosporine in vitro as potential modifiers and these factors may account for their conflicting conclusions. Here we report that peri-operative blood transfusion is associated with an increased risk of AMR, but only in recipients with pre-transplant DSA detected using solid phase assays, all of whom had been previously
exposed to RBCT and other sensitising events. This effect of peri-operative transfusion was not found in recipients without DSA, suggesting that the combination of DSA and peri-operative blood transfusion may be particularly detrimental to the transplanted Rapamycin price graft. Importantly, adverse events after peri-operative blood transfusion included not only antibody mediated rejection, but also poorer long term graft outcome and recipient death, independent of the risk of AMR and Non-AMR, consistent with the findings of O’Brien et al. [28]. In light of our findings it is worth considering the immunological mechanisms whereby blood transfusion could increase the pathogenicity of pre-existing DSA. This might be through direct quantitative or qualitative alterations in antibody or indirectly via specific transfusion factors. Scornik et al. [16] have previously identified that re-exposure to blood in those with prior sensitising events such as transplant or pregnancy elicits a broad antibody response; findings that are consistent with our study.