Quantitation of a Plasma Biomarker Profile for the Early Detection of Gaucher Disease type 1 Patients

Abstract

Aim: Gaucher disease (GD) is caused by a deficiency of the lysosomal enzyme acid β-glucocerebrosidase. Recent metabolomic studies highlighted several new metabolites increased in the plasma of GD patients. We aimed to develop and validate a UPLC–MS/MS method allowing a relative quantitation of lyso-Gb₁ and lyso-Gb₁ analogs -28, -12, -2, +14, +16 and +18 Da in addition to sphingosylphosphorylcholine, N-palmitoyl-O-phosphocholine to study potential correlations with clinical manifestations. Methodology & results: Following solid-phase extraction, plasma samples were evaporated and resuspended in 100 μl of resuspension solution. Three microliter is injected into the UPLC–MS/MS for analysis. Conclusion: All biomarkers studied were increased in GD patients. Significant correlations were observed between specific analogs and hematological, and visceral complications, as well as overall disease severity.

Graphical abstract

Keywords:

• biomarker
• Gaucher disease
• glucosylsphingosine
• lyso-Gb₁
• lyso-Gb₁ analogs
• N-palmitoyl-O-phosphocholineserine
• plasma
• sphingosylphosphorylcholine
• tandem mass spectrometry

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futurescience.com/doi/suppl/10.4155/bio-2021-0242

Acknowledgments

The authors would like to sincerely thank Caroline Barr, Nurse-Coordinator at CR-CHUS, Sherbrooke, QC and Claude Meilleur, Clinical Nurse as well as Clemence Merlen, CHU Sainte-Justine for their involvement in this research project. Finally, they are grateful for the instrumental expertise and continuous support received from Waters Corporation.

Financial & competing interests disclosure

The authors acknowledge Shire/Takeda Pharmaceutical for funding this research project under a collaborative research agreement. C Auray-Blais received research grants and honoraria from Shire/Takeda Pharmaceutical. FE Mercier was paid for an advisory board by Sanofi-Genzyme. F Curado is a clinical project manager for Centogene GmbH. P Bauer is the Chief Genomic Officer at Centogene GmbH. I Menkovic received a student stipend from Shire/Takeda Pharmaceutical. The authors also thank the Faculty of Medicine and Health Sciences at the Université de Sherbrooke for a doctoral student grant for I Menkovic. M Boutin received a salary from Shire/Takeda Pharmaceutical. A Alayoubi and G-É Rivard declare that they have no conflicts of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This research project was approved by the Research Ethics Board (REB) of the Faculty of Medicine and Health Sciences of the Centre hospitalier universitaire de Sherbrooke (CHUS) under the project ID MP-31-2017-1414. Collaborating centers REB also approved the project for their respective centers. Moreover, patients recruited from Centogene were part of the Lyso-Prove project, approved by the Universität Rostock REB under project ID A 2015-0025. Informed consent from all patients and healthy controls were obtained.

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2144/000112170