First exploratory study on the metabolome from plasma exosomes in patients with paroxysmal nocturnal hemoglobinuria
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 thrombo...
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Published in | Thrombosis research Vol. 183; pp. 80 - 85 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Ltd
01.11.2019
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Subjects | |
Online Access | Get full text |
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Summary: | 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.
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).
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.
•First metabolome study in exosomes from Paroxysmal nocturnal hemoglobinuria patients.•PGF2α is differentially detected in exosomes from plasma of patients and controls.•PGF2α could play a role in the propagation of thrombosis in these patients.•Metabolome cargo of exosomes could serve as prognostic biomarker of thrombotic risk. |
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Bibliography: | SourceType-Other Sources-1 content type line 63 ObjectType-Correspondence-1 |
ISSN: | 0049-3848 1879-2472 |
DOI: | 10.1016/j.thromres.2019.10.001 |