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

ABSTRACT: Immune 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 conferred by Thrombopoietin receptor agonists (TPO-RA´s), many patients remain refractory. While the existence of different pathophysiological entities is acknowledged, we are still far from stratifying and understanding ITP, a necessary step in order to provide personalized treatment options. We propose that the platelet proteome may give diagnostic and prognostic insights into the disease. As a proof of principle, we aimed to dissect the potential platelet proteome dynamics in the so-called passive and active pre-clinical ITP mouse models. To do that, 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. Interestingly, we observed that not all proteomic alterations were restored when the platelet count has returned to normal. We discuss the biological processes associated with the proteome dynamics observed. Our results show that profiling the platelet proteome may have great potential to improve the management of ITP in humans.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Platelet, Platelet

SUBMITTER: Patricia Martínez-Botía  

LAB HEAD: Laura Gutiérrez

PROVIDER: PXD028814 | Pride | 2022-08-12

REPOSITORIES: Pride