Platelet-derived extracellular vesicles convey mitochondrial DAMPs in platelet concentrates and their levels are associated with adverse reactions
Genevieve Marcoux
Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada
Equally contributed.Search for more papers by this authorAudrey Magron
Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada
Equally contributed.Search for more papers by this authorCaroline Sut
Université de Lyon, UJM-Saint-Etienne, GIMAP, EA 3064, Saint-Étienne, France
Département Scientifique, Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France
Search for more papers by this authorAudree Laroche
Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada
Search for more papers by this authorSandrine Laradi
Université de Lyon, UJM-Saint-Etienne, GIMAP, EA 3064, Saint-Étienne, France
Département Scientifique, Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France
Search for more papers by this authorHind Hamzeh-Cognasse
Université de Lyon, UJM-Saint-Etienne, GIMAP, EA 3064, Saint-Étienne, France
Search for more papers by this authorIsabelle Allaeys
Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada
Search for more papers by this authorOphelie Cabon
Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada
Search for more papers by this authorAnne-Sophie Julien
Department of Mathematics and Statistic, Université Laval, Quebec City, Québec, Canada
Search for more papers by this authorOlivier Garraud
Université de Lyon, UJM-Saint-Etienne, GIMAP, EA 3064, Saint-Étienne, France
Search for more papers by this authorCorresponding Author
Fabrice Cognasse
Université de Lyon, UJM-Saint-Etienne, GIMAP, EA 3064, Saint-Étienne, France
Département Scientifique, Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France
Equally contributed.Address reprint requests to: Eric Boilard, PhD, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Faculté de Médecine de l'Université Laval, 2705 Laurier Boulevard, Room T1-49, Québec, QC, Canada G1V 4G2; e-mail: [email protected]; or Fabrice Cognasse, PhD, Etablissement Français du Sang Auvergne-Rhône-Alpes, Département Scientifique, 25 Boulevard Pasteur, 42100 Saint-Etienne, France; e-mail: [email protected].
Search for more papers by this authorCorresponding Author
Eric Boilard
Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada
Canadian National Transplantation Research Program, Edmonton, Alberta, Canada
Equally contributed.Address reprint requests to: Eric Boilard, PhD, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Faculté de Médecine de l'Université Laval, 2705 Laurier Boulevard, Room T1-49, Québec, QC, Canada G1V 4G2; e-mail: [email protected]; or Fabrice Cognasse, PhD, Etablissement Français du Sang Auvergne-Rhône-Alpes, Département Scientifique, 25 Boulevard Pasteur, 42100 Saint-Etienne, France; e-mail: [email protected].
Search for more papers by this authorGenevieve Marcoux
Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada
Equally contributed.Search for more papers by this authorAudrey Magron
Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada
Equally contributed.Search for more papers by this authorCaroline Sut
Université de Lyon, UJM-Saint-Etienne, GIMAP, EA 3064, Saint-Étienne, France
Département Scientifique, Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France
Search for more papers by this authorAudree Laroche
Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada
Search for more papers by this authorSandrine Laradi
Université de Lyon, UJM-Saint-Etienne, GIMAP, EA 3064, Saint-Étienne, France
Département Scientifique, Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France
Search for more papers by this authorHind Hamzeh-Cognasse
Université de Lyon, UJM-Saint-Etienne, GIMAP, EA 3064, Saint-Étienne, France
Search for more papers by this authorIsabelle Allaeys
Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada
Search for more papers by this authorOphelie Cabon
Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada
Search for more papers by this authorAnne-Sophie Julien
Department of Mathematics and Statistic, Université Laval, Quebec City, Québec, Canada
Search for more papers by this authorOlivier Garraud
Université de Lyon, UJM-Saint-Etienne, GIMAP, EA 3064, Saint-Étienne, France
Search for more papers by this authorCorresponding Author
Fabrice Cognasse
Université de Lyon, UJM-Saint-Etienne, GIMAP, EA 3064, Saint-Étienne, France
Département Scientifique, Établissement Français du Sang Auvergne-Rhône-Alpes, Saint-Étienne, France
Equally contributed.Address reprint requests to: Eric Boilard, PhD, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Faculté de Médecine de l'Université Laval, 2705 Laurier Boulevard, Room T1-49, Québec, QC, Canada G1V 4G2; e-mail: [email protected]; or Fabrice Cognasse, PhD, Etablissement Français du Sang Auvergne-Rhône-Alpes, Département Scientifique, 25 Boulevard Pasteur, 42100 Saint-Etienne, France; e-mail: [email protected].
Search for more papers by this authorCorresponding Author
Eric Boilard
Department of Infectious Diseases and Immunity, Centre de Recherche du CHU de Québec - Université Laval, Quebec City, Québec, Canada
Canadian National Transplantation Research Program, Edmonton, Alberta, Canada
Equally contributed.Address reprint requests to: Eric Boilard, PhD, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Faculté de Médecine de l'Université Laval, 2705 Laurier Boulevard, Room T1-49, Québec, QC, Canada G1V 4G2; e-mail: [email protected]; or Fabrice Cognasse, PhD, Etablissement Français du Sang Auvergne-Rhône-Alpes, Département Scientifique, 25 Boulevard Pasteur, 42100 Saint-Etienne, France; e-mail: [email protected].
Search for more papers by this authorAbstract
BACKGROUND
Whereas platelet transfusion is a common medical procedure, inflammation still occurs in a fraction of transfused individuals despite the absence of any apparent infectious agents. Platelets can shed membrane vesicles, called extracellular vesicles (EVs), some of which contain mitochondria (mito+EV). With its content of damage-associated molecular pattern (DAMP), the mitochondrion can stimulate the innate immune system. Mitochondrial DNA (mtDNA) is a recognized DAMP detected in the extracellular milieu in numerous inflammatory conditions and in platelet concentrates. We hypothesized that platelet-derived mitochondria encapsulated in EVs may represent a reservoir of mtDNA.
STUDY DESIGN AND METHODS
Herein, we explored the implication of mito+EVs in the occurrence of mtDNA quantified in platelet concentrate supernatants that induced or did not induce transfusion adverse reactions.
RESULTS
We observed that EVs were abundant in platelet concentrates, and platelet-derived mito+EVs were more abundant in platelet concentrates that induced adverse reactions. A significant correlation (rs = 0.73; p < 0.0001) between platelet-derived mito+EV levels and mtDNA concentrations was found. However, there was a nonsignificant correlation between the levels of EVs without mitochondria and mtDNA concentrations (rs = −0.11; p = 0.5112). The majority of the mtDNA was encapsulated into EVs.
CONCLUSION
This study suggests that platelet-derived EVs, such as those that convey mitochondrial DAMPs, may be a useful biomarker for the prediction of potential risk of adverse transfusion reactions. Moreover, our work implies that investigations are necessary to determine whether there is a causal pathogenic role of mitochondrial DAMP encapsulated in EVs as opposed to mtDNA in solution.
CONFLICT OF INTEREST
The authors declare no conflicts of interest.
Supporting Information
| Filename | Description |
|---|---|
| trf15300-sup-0001-supinfo.docxWord 2007 document , 45.6 KB |
Appendix S1. Supplementary methods. Table S1. Adverse transfusion reaction–associated platelet concentrates. Table S2. Qualitative information of the transfusion product. Table S3. Quantitative information on the donors and on the platelet concentrates. Table S4. Quantification of EV subtype in platelet concentrates. Table S5. Cubic effect of EVs on adverse reaction. Table S6. Predictive values of EVs subtypes adjusted for the different adverse reaction. Table S7. EV subtype associations with mitochondrial DNA in platelet concentrates (n = 35) |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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