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dc.contributor.authorSaris, Anno
dc.contributor.authorPeyron, Ivan
dc.contributor.authorVan Der Meer, Pieter F.
dc.contributor.authorStuge, Tor Brynjar
dc.contributor.authorZwaginga, Jaap Jan
dc.contributor.authorvan Ham, S Marieke
dc.contributor.authorten Brinke, Anja
dc.date.accessioned2019-03-08T13:26:01Z
dc.date.available2019-03-08T13:26:01Z
dc.date.issued2018-06-05
dc.description.abstractPlatelet transfusion can elicit alloimmune responses leading to alloantibody formation against donor-specific polymorphic residues, ultimately resulting in platelet transfusion refractoriness. Universal leukoreduction significantly reduced the frequency of alloimmunization after platelet transfusion, thereby showing the importance of white blood cells (WBCs) in inducing this alloresponse. It is, however, unknown if the residual risk for alloimmunization is caused by WBCs remaining after leukoreduction or if alloimmunization can be induced by platelets themselves. This study investigated the capacity of platelets to induce alloimmunization and identified potential product-related risk factors for alloimmunization. First, internalization of allogeneic platelets by dendritic cells (DCs) was demonstrated by confocal microscopy. Second, after internalization, presentation of platelet-derived peptides was shown by mass spectrometry analysis of human leukocytes antigen (HLA)-DR eluted peptides. Third, platelet-loaded DCs induced platelet-specific CD4 T cell responses. Altogether, this indicates a platelet-specific ability to induce alloimmunization. Therefore, factors enhancing platelet internalization may be identified as risk factor for alloimmunization by platelet concentrates. To investigate if storage of platelets is such a risk factor, internalization of stored platelets was compared with fresh platelets and showed enhanced internalization of stored platelets. Storage-induced apoptosis and accompanied phosphatidylserine exposure seemed to be instrumental for this. Indeed, DCs pre-incubated with apoptotic platelets induced the strongest IFN-γ production by CD4 T cells compared with pre-incubation with untreated or activated platelets. In conclusion, this study shows the capacity of platelets to induce platelet-specific alloimmune responses. Furthermore, storage-induced apoptosis of platelets is identified as potential risk factor for alloimmunization after platelet transfusions.en_US
dc.description.sponsorshipSanquin internal fundingen_US
dc.descriptionThe following article, Saris, A., Peyron, I., van Der Meer, P.F., Stuge, T.B., Zwaginga, J.J., van Ham, S.M. & ten Brinke, A. (2018). Storage-induced platelet apoptosis is a potential risk factor for alloimmunization upon platelet transfusion. <i>Frontiers in Immunology, 9</i>, can be accessed at <a href=https://doi.org/10.3389/fimmu.2018.01251> https://doi.org/10.3389/fimmu.2018.01251</a>.en_US
dc.identifier.citationSaris, A., Peyron, I., van Der Meer, P.F., Stuge, T.B., Zwaginga, J.J., van Ham, S.M. & ten Brinke, A. (2018). Storage-induced platelet apoptosis is a potential risk factor for alloimmunization upon platelet transfusion. <i>Frontiers in Immunology, 9</i>. https://doi.org/10.3389/fimmu.2018.01251en_US
dc.identifier.cristinIDFRIDAID 1629719
dc.identifier.doi10.3389/fimmu.2018.01251
dc.identifier.issn1664-3224
dc.identifier.urihttps://hdl.handle.net/10037/14917
dc.language.isoengen_US
dc.publisherFrontiers Mediaen_US
dc.relation.journalFrontiers in Immunology
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.subjectplateleten_US
dc.subjecttransfusion medicineen_US
dc.subjectalloimmunizationen_US
dc.subjectstorageen_US
dc.subjectinternalizationen_US
dc.subjectantigen presentationen_US
dc.titleStorage-induced platelet apoptosis is a potential risk factor for alloimmunization upon platelet transfusionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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