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Platelet Proteomics to Understand the Pathophysiology of Immune Thrombocytopenia: Studies in Mouse Models

dc.contributor.authorMartínez-Botía, Patricia
dc.contributor.authorMeinders, Marjolein
dc.contributor.authorDe Cuyper, Iris M.
dc.contributor.authorEble, Johannes A.
dc.contributor.authorSemple, John W.
dc.contributor.authorGutiérrez Gutiérrez, Laura
dc.identifier.citationBlood Advances (2022); doi:10.1182/bloodadvances.2021006438
dc.description.abstractImmune thrombocytopenia (ITP) is an autoimmune disease characterized by enhanced platelet clearance and defective platelet production. Diagnosis by exclusion and "trial-error" treatment strategies are common practice, and despite the advancement in treatment options, many patients remain refractory. While the existence of different pathophysiological entities is acknowledged, we are still far from stratifying and understanding ITP. To deepen into this, we aimed to dissect the platelet proteome dynamics in the so-called passive and active pre-clinical ITP mouse models, which we propose to phenocopy respectively acute/newly diagnosed and persistent/chronic stages of ITP in human. We obtained the platelet proteome at the thrombocytopenic stage and upon platelet count recovery (reached naturally or upon IVIg-treatment, depending on the model). While most of the proteomic alterations were common to both ITP models, there were model-specific protein dynamics, which accompanied and explained alterations in platelet aggregation responses, as measured in the passive ITP model. Interestingly, the expression dynamics observed in Syk, may explain, extrapolated to human and pending validation, the increased bleeding tendency of ITP patients when treated with Fostamatinib as third-or-later-line, as opposed to second-line treatment. We propose that the platelet proteome may give diagnostic/prognostic insights into ITP, and such studies should be pursued in
dc.description.sponsorshipThis work was partially supported the Center for Translational Molecular Medicine (, project Innovative Coagulation Diagnostics (INCOAG, grant 01C-201), and the Dutch Heart Foundation, an RYC fellowship (RYC-199 2013-12587; Ministerio de Economía y Competitividad, Spain) and an I+D 2017 grant (SAF2017-85489-P; Ministerio de Ciencia, Innovación y Universidades, Spain and Fondos FEDER) to L.G. and a Severo Ochoa Grant (PA-20-PF-BP19-014; Consejería de Ciencia, Innovación y Universidades del Principado de Asturias, Spain) to P.M.-B. JAE is financially supported by the Interdisciplinary Center for Clinical Research (IZKF) of University of Münster (grant: IZKF: Ebl4/009/21).spa
dc.relation.ispartofBlood Advspa
dc.rights© 2022 American Society of Hematology*
dc.titlePlatelet Proteomics to Understand the Pathophysiology of Immune Thrombocytopenia: Studies in Mouse Modelsspa
dc.relation.projectIDMINECO/RYC-199 2013-12587

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