Geomic and proteomic study of platelet concentrates that induced transfusion reactions ; Étude génomique et protéomique des concentrés plaquettaires ayant induit une réaction post-transfusionnelle
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Media type:
E-Book
Title:
Geomic and proteomic study of platelet concentrates that induced transfusion reactions ; Étude génomique et protéomique des concentrés plaquettaires ayant induit une réaction post-transfusionnelle
imprint:
[Erscheinungsort nicht ermittelbar]: HAL CCSD, 2016
Language:
French
Origination:
University thesis:
Dissertation, HAL CCSD, 2016
Footnote:
Description:
Despite the implementation of systematic leucoreduction, platelet transfusions are still generating transfusion reactions (also called Adverse Events or AEs"). We know that platelets release proinflammatory molecules during preparation and storage of platelet components (PCs) notably the soluble CD40 ligand or sCD40L and high levels are associated with AEs. In this thesis, we aimed to understand the mechanisms of occurrence of inflammatory platelet transfusion reactions. In the first part, we investigated the genetic polymorphisms of CD40LG. We failed to identify a significant association with AEs but we identified genetic markers of sCD40L overexpression: a CD40LG haplotype and also an interchromosomal haplotype (CD40LG-CD40-ITGA2). However, these haplotypes have not been found to be associated with AEs. In the second part, we showed that, during storage of non leucoreduced PCs, leukocyte-derived "biological response modifiers" (BRMs) dominate and influence the platelet-derived BRMs. Then, we found increased levels of another individualized BRM in PCs involved in AEs: mitochondrial DNA, classified as an endogenous danger-associated molecular pattern (DAMP). In the last part, we performed an integrated proteomic and transcriptomic study by LC-MS/MS and RNA-seq, respectively, to better understand the pathophysiology of AEs in a case-control approach. The biological enrichment of differentially expressed genes revealed a significant association with platelet activation, apoptosis and inflammatory mechanisms which may be involved in platelet transfusion reactions. This study provides novel insights into the molecular mechanisms underlying the occurrence of AEs and could give paths to prevent them