Impact of Allogeneic Blood Transfusion on Primary Graft Dysfunction and Immune Modulation in Lung Transplantation 2350

Abstract Description A recent study highlights a significant links between allogeneic blood transfusions (allo-BT) and primary graft dysfunction (PGD) following lung transplantation, though the underlying mechanisms remain unclear. Ischemia-reperfusion injury (IRI) is a well-established risk factor for PGD, and our prior research using a mouse orthotopic lung transplant model underscored the critical role of monocytes in IRI progression. We hypothesized that allo-BT might worsen IRI by activating monocytes and/or inducing antibody production. Using a mouse model of IRI induced by hilar clamping, we observed that administering allo-BT three days before IRI markedly aggravated lung injury. This was evidenced by increased neutrophil infiltration and impaired arterial blood gas levels. Moreover, allo-BT led to a rise in classical monocytes within the lung and elevated plasma IL-1β levels, indicating that transfusion-related injury may be driven by monocyte infiltration and the release of pro-inflammatory cytokines from activated monocytes. Interestingly, when allo-BT was administered 14 days before IRI, lung injury remained exacerbated compared to syngeneic blood transfusion. However, in this case, plasma IL-1β levels were unaffected, and non-donor-specific anti-MHC antibodies were detected. These findings suggest that non-donor-specific antibodies could contribute to early post-transplant complications, providing a complementary perspective to the traditional focus on donor-specific HLA antibodies. Funding Sources Supported by National Heart, Lung, and Blood Institute 5R01HL153312-04; 2R01HL145478-06; P01/FP00002771. Topic Categories Transplantation Immunology (TRAN)