Dissecting platelet proteomics to understand the pathophysiology of immune thrombocytopenia : studies in mouse models

Martínez-Botía, PatriciaInstituto de Investigación Sanitaria del Principado de Asturias (ISPA) (författare)

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by enhanced platelet clearance and defective platelet production. Diagnosis by exclusion and trial-and-error treatment strategies is common practice, and despite the advancement in treatment options, many patients remain refractory. Although the existence of different pathophysiological entities is acknowledged, we are still far from stratifying and understanding ITP. To investigate, we sought to dissect the platelet proteome dynamics in so-called passive and active preclinical ITP mouse models, with which we propose to phenocopy respectively acute/newly diagnosed and persistent/chronic stages of ITP in humans. We obtained the platelet proteome at the thrombocytopenic stage and after platelet count recovery (reached naturally or by IVIg-treatment, depending on the model). Although most of the proteomic alterations were common to both ITP models, there were model-specific protein dynamics that accompanied and explained alterations in platelet aggregation responses, as measured in the passive ITP model. The expression dynamics observed in Syk may explain, extrapolated to humans and pending validation, the increased bleeding tendency of patients with ITP when treated with fostamatinib as third or later- as opposed to second line of treatment. We propose that the platelet proteome may give diagnostic and prognostic insights into ITP and that such studies should be pursued in humans.

Meinders, MarjoleinAcademic Medical Center of University of Amsterdam (AMC),Sanquin Research (författare)
De Cuyper, Iris MSanquin Research,Academic Medical Center of University of Amsterdam (AMC) (författare)
Eble, Johannes AUniversity of Münster (författare)
Semple, John WLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Region Skåne(Swepub:lu)jo0201se (författare)
Gutiérrez, LauraSanquin Research,Academic Medical Center of University of Amsterdam (AMC),University of Oviedo,Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) (författare)
Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)Academic Medical Center of University of Amsterdam (AMC) (creator_code:org_t)

Ingår i:Blood Advances: American Society of Hematology6:11, s. 3529-35342473-95292473-9537

Av författaren/redakt...: Martínez-Botía, ...; Meinders, Marjol ...; De Cuyper, Iris ...; Eble, Johannes A; Semple, John W; Gutiérrez, Laura

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Hematologi

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