Abstract Number: OC 06.5
Meeting: ISTH 2020 Congress
Background: Transfusion-related acute lung injury (TRALI) remains a major cause of transfusion-related fatalities. TRALI can be provoked by transfusion of blood products containing allogeneic antibodies targeting cells of the recipient. The involvement of Fcγ receptors in this type of TRALI has been poorly assessed. FcγRIIA/CD32A is an activating low affinity receptor for IgGs expressed on human platelets and immune cells, whereas no corresponding ortholog is present in mice.
Aims: Evaluate the contribution of CD32A in a model of immunological TRALI in transgenic mice expressing this human receptor.
Methods: Antibody‐mediated TRALI was induced in control mice (WT) and mice transgenic for human CD32A (CD32A+) by lipopolysaccharide priming followed by administration of a recombinant humanized anti-MHC I monoclonal antibody (derived from clone 34-1-2S).
Results: TRALI responses were more severe in CD32A+ than in WT mice in terms of pulmonary edema and mortality, which reached 90% in CD32A+ versus 40% in WT animals (n=10, **p=0.0027, log-rank test). Soon after induction of TRALI, the drop in platelet count worsened in CD32A+ compared to WT mice. Moreover, massive release of platelet granule contents was observed only in the peripheral blood of CD32A+ animals. Preventive platelet depletion suppressed the exacerbation of TRALI observed in CD32A+ mice, whereas it did not impact TRALI in the WT. Long term treatment with the selective serotonin reuptake inhibitor fluoxetine, to deplete the serotonin content of platelet granules, selectively abolished the aggravation of lung edema in CD32A+ mice. Blockade of 5-hydroxytryptamine 2A receptors with sarpogrelate also prevented the exacerbation of this edema in CD32A+ animals when the drug was administered before and after the induction of TRALI.
Conclusions: Our findings identify platelet CD32A as a critical determinant of the severity of antibody-mediated TRALI and provide a rationale for the design of serotonin pathway targeting strategies to attenuate immunological TRALI in patients.
To cite this abstract in AMA style:El Mdawar M-, Maître B, Magnenat S, Tupin F, Jonsson F, Gachet C, de la Salle H, Hechler B. Platelets Expressing FcγRIIA/CD32A Determine the Severity of Immunological Transfusion-Related Acute Lung Injury in Mice [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/platelets-expressing-fc%ce%b3riia-cd32a-determine-the-severity-of-immunological-transfusion-related-acute-lung-injury-in-mice/. Accessed May 6, 2021.
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