[31] Qian et al. [32] have shown in a cardiac rodent model that pre-sensitisation with allogeneic RBCT causes accelerated graft rejection in the presence of complement and antibody binding to graft endothelium. Complement activation products and

quantitative changes in cytokines may be present within stored blood products [33] and [34]. Norda and colleagues found that stored plasma components may differ significantly in the amount and timing of complement activation JQ1 in vitro products, particularly C3a, which could specifically trigger pathological changes if pre-existing effector DSA is present. Theoretically cytokines and other factors present in blood products could also induce non-complement activating ALK inhibitor DSA to class switch to IgG1 and/or IgG3 complement activating

antibodies. Mice models of transfusion related acute lung injury suggest that MHC class I specific antibody binding to nonhematopoietic cells drives complement activation and production of reactive oxygen species [35]. T cell allorecognition of allogeneic HLA molecules, present even in leucodepleted blood products, may be associated with specific and non-specific immune activation including increased cytokine production and cytotoxicity function. Whether exposure to RBCT in sensitised patients stimulates an increase in the absolute amount or breadth of DSA and/or class switching and complement binding was beyond the

scope of this study. Serially monitoring these changes would be informative however the frequency of sampling and interventions for management of rejection which alter antibody measurement confound interpretation. These putative adverse effects of peri-operative blood transfusion could be investigated further using in-vivo animal models. This data suggests that avoidance of peri-operative blood transfusion or, given the impossibility of eliminating all transfusion risk, establishing a new paradigm for RBCT in sensitised transplant recipients why should be considered. It is established that leucodepleted unmatched RBCT does not reduce sensitisation [23] and therefore selecting HLA matched blood with its significantly reduced risk of HLA specific antibody production may be particularly suited to patients with DSA [36]. The use of HLA matched blood transfusion products for renal transplantation patients is feasible and may be effective within a clinical setting [36] and [37]. Furthermore recipients with high levels of sensitization may even benefit from pre-operative storage of autologous blood products for use in the event of requiring a peri-operative blood transfusion [38].