Project description:Mechanisms underlying variability in patient’s responses to platelet transfusions are not fully understood. To characterize platelet transfusion induced changes on plasma proteins, we used plasma proteomics to study the effect of 1) autologous platelet transfusions in healthy volunteers in absence and presence of controlled endotoxemia, and of 2) allogenic platelet transfusions in haemato-oncologic patients. Longitudinal plasma profiling revealed intra-individual variation in healthy volunteers, but no impact of autologous transfusions. Controlled endotoxemia induced by lipopolysaccharide (LPS) exposure in healthy volunteers elicited a shared acute phase response across all recipients, which was characterized by increased abundance of two distinct protein clusters. However, this did not result in transfusion-specific responses on plasma protein levels. Likewise, plasma proteomic profiling of paired samples from haemato-oncological patients prior- and post-administration of allogenic transfusions revealed intra-individual variation and a transfusion-specific response that remained limited to platelet basic protein (PPBP). We found a positive association of haptoglobin levels (HP, ρ = 0.61) and a negative association of extracellular superoxide dismutase [Cu-Zn] levels (SOD3, ρ = -0.62) prior transfusion to corrected count increments (CCI) at 1h and 24h, respectively. Taken together, platelet transfusions did not induce specific changes in plasma protein levels in controlled endotoxemia but were associated with increased levels of platelet-associated proteins in haemato-oncological patients. Importantly, no additional changes in plasma protein profiles, which could be associated with inflammation or dysregulated processes, were observed following platelet transfusions.
Project description:Blood platelets destined for transfusion release panoply of molecules during preparation and storage. The leukoreduction process made the transfusion safer but did not completely abolish the adverse events. The rationale is to study the proteome profile of platelet components SDA-PC (platelet pellets) involved in transfusion adverse events.
Project description:Blood platelets destined for transfusion release panoply of molecules during preparation and storage. The leukoreduction process made the transfusion safer but did not completely abolish the adverse events. The rationale is to study the proteome profile of platelet components PPC (platelet pellets) involved in transfusion adverse events.
Project description: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.
Project description:Genotypic and phenotypic characteristics of Escherichia coli involved in transfusion transmitted bacterial infections:implications for preventive strategies
Project description:We report a transfusion-transmitted hepatitis A virus infection in an immunocompromised patient in France, detected shortly after a transfusion of pathogen-reduced pooled platelets. This case raises questions about the efficacy of donor screening methods. Additional safety measures, such as routine donation screening, should be considered.
Project description:The purpose of this study is to determine if there is an association between hepatitis C infection and kidney cancer. All patients who are diagnosed with kidney cancer and who will either have a biopsy or surgery will be offered to be tested for hepatitis C. The control group will be colon cancer patients. Both groups would be of recent diagnosis (6 months).
