Allogeneic red blood cell transfusion impairs antigen presentation and stimulates inflammatory response

Allogeneic red blood cell transfusion increases risk of infection and organ injury, which we here attempted to explain by analyzing gene expression in various types of immune cells. We prospectively compared adverse events and transcriptomic profiles in immune cells between patients who received transfusion of red blood cells (not plasma or platelets) during or after on-pump cardiac surgery and patients who did not. The composite rate of adverse events was significantly more frequent among patients who received transfusions (4 of 16, 25%) than among those who did not (3 of 60, 5%, p = 0.03). Transfusion downregulated in monocytes several genes involved in antigen presentation, such as HLA-DQA2 and HLA-DPB1, as well as several ligand-receptor pairs linking monocytes to natural killer cells (HLA-C-KIR2DL1, HLA-E-CD94:NKG2A) and T cells (CD28-CD86, CD2-CD58) for antigen presentation. Transfusion upregulated the early activation marker CD69 and pro-inflammatory and chemotactic factors (IL-6, TNFR1, TNFR2, CXCL9 and CCL3) in T, B and natural killer cells. Transfusion volume correlated positively with the percentage of CD69+ CD8+ T cells, which in turn correlated positively with composite risk of adverse events. Our findings may help explain how transfusion causes immunosuppression and systemic inflammation, thereby increasing risk of adverse events. Our work may provide clues to developing preventive or mitigating measures in order to optimize prognosis of patients who receive blood cell transfusions. Overall design: We performed single-cell RNA sequencing of peripheral blood mononuclear cells from two patients in the exploration phase who received RBC transfusion(Trans-RBC) and three who did not (No-Trans) at Pre-surgery and at End CPB. The sequencing profiles were used to cluster the cells into the following four immune cell types based on expression of well-established markers: monocytes, T cells, B cells, and natural killer cells.