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Quantitative proteomics of plasma vesicles identify novel biomarkers for Hemoglobin E/ β-Thalassemic patients

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)95-104
Number of pages10
JournalBlood Advances
Volume2
Issue number2
Early online date16 Jan 2018
DOIs
DateAccepted/In press - 16 Dec 2017
DateE-pub ahead of print - 16 Jan 2018
DatePublished (current) - Feb 2018

Abstract

Hemoglobin (Hb) E/β-thalassemia has a wide spectrum of clinical manifestations that cannot be explained purely by its genetic background. Circulating extracellular vesicles (EVs) are one factor that likely contributes to disease severity. This study has explored the differences in protein composition and quantity between EVs from HbE/β-thalassemic patients and normal healthy individuals. We used Tandem Mass Tag (TMT) labeling mass spectrometry to analyze the EV proteins isolated from the plasma of 15 patients compared to the controls. To reduce biological variation between individuals, the EV proteins isolated from randomly assigned groups of 5 HbE/β-thalassemic patients were pooled and compared to 5 pooled age, and gender-matched controls, in 3 separate experiments. Alpha hemoglobin stabilizing protein had the highest fold increase. Catalase, superoxide dismutase, T-complex proteins, heat shock proteins, transferrin receptor, ferritin, and cathepsin S were also up-regulated in thalassemic circulating EVs. Importantly, haptoglobin and hemopexin were consistently reduced in patients’ EVs across all data sets, in keeping with the existing hemolysis that occurs in thalassemia. The proteomic data analysis of EVs samples isolated from 6 individual HbE/β-thalassemic patients and western blotting results corroborated these findings. In conclusion, we have successfully identified consistent alterations of protein quantity between EVs from HbE/β-thalassemic and normal individuals. This work highlights haptoglobin, hemopexin, and cathepsin S as potential clinically relevant biomarkers for levels of hemolysis and inflammation. Monitoring of these plasma proteins could help in the clinical management of thalassemia.

    Research areas

  • Thalassemia, Microvesicles, Proteomics

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via ASH at http://www.bloodadvances.org/content/2/2/95 . Please refer to any applicable terms of use of the publisher.

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