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Antigen Density Dictates Immune Responsiveness following Red Blood Cell Transfusion.

ABSTRACT: Although RBC transfusion can result in the development of anti-RBC alloantibodies that increase the probability of life-threatening hemolytic transfusion reactions, not all patients generate anti-RBC alloantibodies. However, the factors that regulate immune responsiveness to RBC transfusion remain incompletely understood. One variable that may influence alloantibody formation is RBC alloantigen density. RBC alloantigens exist at different densities on the RBC surface and likewise exhibit distinct propensities to induce RBC alloantibody formation. However, although distinct alloantigens reside on the RBC surface at different levels, most alloantigens also represent completely different structures, making it difficult to separate the potential impact of differences in Ag density from other alloantigen features that may also influence RBC alloimmunization. To address this, we generated RBCs that stably express the same Ag at different levels. Although exposure to RBCs with higher Ag levels induces a robust Ab response, RBCs bearing low Ag levels fail to induce RBC alloantibodies. However, exposure to low Ag-density RBCs is not without consequence, because recipients subsequently develop Ag-specific tolerance. Low Ag-density RBC-induced tolerance protects higher Ag-density RBCs from immune-mediated clearance, is Ag specific, and occurs through the induction of B cell unresponsiveness. These results demonstrate that Ag density can potently impact immune outcomes following RBC transfusion and suggest that RBCs with altered Ag levels may provide a unique tool to induce Ag-specific tolerance.

SUBMITTER: Arthur CM

PROVIDER: S-EPMC5777137 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Antigen Density Dictates Immune Responsiveness following Red Blood Cell Transfusion.

Arthur Connie M CM Patel Seema R SR Smith Nicole H NH Bennett Ashley A Kamili Nourine A NA Mener Amanda A Gerner-Smidt Christian C Sullivan Harold C HC Hale J Scott JS Wieland Andreas A Youngblood Benjamin B Zimring James C JC Hendrickson Jeanne E JE Stowell Sean R SR

Journal of immunology (Baltimore, Md. : 1950) 20170301 7

Although RBC transfusion can result in the development of anti-RBC alloantibodies that increase the probability of life-threatening hemolytic transfusion reactions, not all patients generate anti-RBC alloantibodies. However, the factors that regulate immune responsiveness to RBC transfusion remain incompletely understood. One variable that may influence alloantibody formation is RBC alloantigen density. RBC alloantigens exist at different densities on the RBC surface and likewise exhibit distinc ...[more]

PMID: 28250159

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Project description:Background The relationship between local hospital culture and transfusion rates following endovascular and surgical cardiovascular procedures has not been well studied. Methods and Results Patients undergoing coronary revascularization, aortic valve replacement, lower extremity peripheral vascular intervention, or carotid artery revascularization from up to 852 US hospitals in the Nationwide Readmissions Database were identified. Crude and risk-standardized red blood cell transfusion rates were determined for each procedure. Pearson correlation coefficients were calculated between respective procedural transfusion rates. Median odds ratios were estimated to reflect between-hospital variability in red blood cell transfusion rates following the same procedure for a given patient. There was wide variation in red blood cell transfusion rates across different procedures, from 2% following carotid endarterectomy to 29% following surgical aortic valve replacement. For surgical and endovascular modalities, transfusion rates at the same hospital were highly correlated for aortic valve replacement (r=0.67; P<0.001), moderately correlated for coronary revascularization (r=0.56; P<0.001) and peripheral vascular intervention (r=0.51; P<0.001), and weakly correlated for carotid artery revascularization (r=0.19, P<0.001). Median odds ratios were all >2, highest for coronary artery bypass graft surgery and surgical aortic valve replacement, indicating substantial site variation in transfusion rates. Conclusions After adjustment for patient-related factors, wide variation in red blood cell transfusion rates remained across surgical and endovascular procedures employed for the same cardiovascular condition. Transfusion rates following these procedures are highly correlated at individual hospitals and vary widely across hospitals. In aggregate, these findings suggest that local institutional culture significantly influences the decision to transfuse following invasive cardiovascular procedures and highlight the need for randomized data to inform such decisions.

Project description:ImportanceRed blood cell (RBC) transfusion is common among patients admitted to the intensive care unit (ICU). Despite multiple randomized clinical trials of hemoglobin (Hb) thresholds for transfusion, little is known about how these thresholds are incorporated into current practice.ObjectiveTo evaluate and describe ICU RBC transfusion practices worldwide.Design, setting, and participantsInternational, prospective, cohort study that involved 3643 adult patients from 233 ICUs in 30 countries on 6 continents from March 2019 to October 2022 with data collection in prespecified weeks.ExposureICU stay.Main outcomes and measuresThe primary outcome was the occurrence of RBC transfusion during ICU stay. Additional outcomes included the indication(s) for RBC transfusion (consisting of clinical reasons and physiological triggers), the stated Hb threshold and actual measured Hb values before and after an RBC transfusion, and the number of units transfused.ResultsAmong 3908 potentially eligible patients, 3643 were included across 233 ICUs (median of 11 patients per ICU [IQR, 5-20]) in 30 countries on 6 continents. Among the participants, the mean (SD) age was 61 (16) years, 62% were male (2267/3643), and the median Sequential Organ Failure Assessment score was 3.2 (IQR, 1.5-6.0). A total of 894 patients (25%) received 1 or more RBC transfusions during their ICU stay, with a median total of 2 units per patient (IQR, 1-4). The proportion of patients who received a transfusion ranged from 0% to 100% across centers, from 0% to 80% across countries, and from 19% to 45% across continents. Among the patients who received a transfusion, a total of 1727 RBC transfusions were administered, wherein the most common clinical indications were low Hb value (n = 1412 [81.8%]; mean [SD] lowest Hb before transfusion, 7.4 [1.2] g/dL), active bleeding (n = 479; 27.7%), and hemodynamic instability (n = 406 [23.5%]). Among the events with a stated physiological trigger, the most frequently stated triggers were hypotension (n = 728 [42.2%]), tachycardia (n = 474 [27.4%]), and increased lactate levels (n = 308 [17.8%]). The median lowest Hb level on days with an RBC transfusion ranged from 5.2 g/dL to 13.1 g/dL across centers, from 5.3 g/dL to 9.1 g/dL across countries, and from 7.2 g/dL to 8.7 g/dL across continents. Approximately 84% of ICUs administered transfusions to patients at a median Hb level greater than 7 g/dL.Conclusions and relevanceRBC transfusion was common in patients admitted to ICUs worldwide between 2019 and 2022, with high variability across centers in transfusion practices.

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Antigen Density Dictates Immune Responsiveness following Red Blood Cell Transfusion.

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Antigen Density Dictates Immune Responsiveness following Red Blood Cell Transfusion.

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