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Thromb Res. 2019 Nov;183:80-85. doi: 10.1016/j.thromres.2019.10.001. Epub 2019 Oct 28.

First exploratory study on the metabolome from plasma exosomes in patients with paroxysmal nocturnal hemoglobinuria.

Author information

1
Servicio de Metabolómica, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, Spain.
2
Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain; Grupo de Investigación CB15/00055, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
3
Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain.
4
Laboratory of Food & Health, Group of Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, Spain. Electronic address: jcespin@cebas.csic.es.
5
Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain; Grupo de Investigación CB15/00055, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Electronic address: immlgi@um.es.

Abstract

INTRODUCTION:

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease in which patients are at increased risk of thrombosis. The mechanisms underlying the associated thrombosis risk are still poorly understood, although it is known that Eculizumab, the drug of choice for symptomatic patients, prevents thrombotic events. Exosomes are extracellular vesicles that can carry and disseminate genetic material, tumor biomarkers and inflammatory mediators. To date, the metabolite cargo of plasma exosomes from PNH patients has not yet been explored. In this pilot trial, we compared the metabolome of plasma exosomes from PNH patients with that of healthy subjects in order to provide further insights into this rare disease.

RESULTS:

We used a non-targeted metabolomics approach with UPLC-ESI-QTOF-MS/MS and GC-MS platforms. Multivariate analyses revealed the differential occurrence (p < .001) of 78 metabolites in plasma exosomes from PNH patients vs healthy control subjects. Remarkably, prostaglandin F2-alpha (6.1-fold), stearoyl arginine (5.3-fold) and 26-hydroxycholesterol-3-sulfate (11.2-fold) were higher in PNH patients vs healthy controls (p < .001).

CONCLUSIONS:

This is the first description on the differential metabolite cargo occurring in plasma exosomes from PNH patients. Our results could contribute to the search for possible prognostic biomarkers of thrombotic risk in patients with PNH. Further research in a larger cohort to validate these results is warranted.

KEYWORDS:

Exosomes; Hemoglobinuria; Hydroxycholesterol-3-sulfate; Metabolome; Prostaglandin F2-alpha; Stearoyl arginine

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