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Etiopathologie du TRALI (Transfusion-Related Acute Lung Injury) : anticorps anti-HLA et NADPH oxydase phagocytaire

Abstract : TRALI represents an acute non-cardiogenic pulmonary oedema following blood transfusion. The unknown etiopathological mechanism of TRALI leads to an underestimation of the incidence. Clinical and anatomical studies highlighted the major role of neutrophils (PMN) and showed that TRALI results from an increased number of neutrophils within the pulmonary capillary endothelium. Many evidence suggest that antibodies recognizing human leukocyte antigens (HLA) present in the blood transfusion are the predominant trigger leading to TRALI. Towards theses findings, we investigated the precise mechanism in TRALI in order to get a better knowledge of its diagnosis, its prevention and the patient care. We confirm the major role of anti-HLA antibodies and validate for the first time the two-hit model: the first-hit related to the patient clinical condition leads to their PMN stimulation, followed in the second-hit by the infusion of blood products containing anti-HLA antibodies that activate the phagocytic NADPH oxidase. This event induces PMN activation and the release of reactive oxygen species that are directly responsible for the pulmonary endothelial damage and cause the endothelial permeability increase. We also demonstrate the cut-off of anti-HLA antibodies that raises PMN activation. Finally, we showed that both the antigen-binding and the Fc-binding systems to antibodies are needed to induce a major PMN activation. We found that the binding of anti-HLA antibodies to HLA antigens promote the formation of cluster of Fc receptors within lipid rafts. The translocation of Fc receptors into lipid rafts improve Fc receptors activation, leading to intracellular signal transduction and activation of effector functions, such as NADPH oxidase activation and release of reactive oxygen species involved in tissue damage.
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https://tel.archives-ouvertes.fr/tel-01690690
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Submitted on : Tuesday, January 23, 2018 - 12:06:08 PM
Last modification on : Friday, October 23, 2020 - 5:04:40 PM
Long-term archiving on: : Thursday, May 24, 2018 - 10:56:19 AM

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  • HAL Id : tel-01690690, version 1

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Kathy Khoy. Etiopathologie du TRALI (Transfusion-Related Acute Lung Injury) : anticorps anti-HLA et NADPH oxydase phagocytaire. Hématologie. Université Grenoble Alpes, 2016. Français. ⟨NNT : 2016GREAV041⟩. ⟨tel-01690690⟩

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