Tissue and plasma globotriaosylsphingosine could be a biomarker for assessing enzyme replacement therapy for Fabry disease

Togawa, Tadayasu; Kawashima, Ichiro; Kodama, Takashi; Tsukimura, Takahiro; Suzuki, Toshihiro; Fukushige, Tomoko; Kanekura, Takuro; Sakuraba, Hitoshi

doi:10.1016/j.bbrc.2010.08.006

Cited by 38 publications

(44 citation statements)

References 22 publications

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“…Here we present a new method for the quantification of lysoGb3 based on ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) and the use of [5,6,7,8,9] 13 C 5 -labeled lysoGb3 as the internal standard, which was synthesized for this particular purpose. In addition, we quantify a compound closely related to lysoGb3, lyso-ene-Gb3.…”

confidence: 99%

“…1 Nonlabeled lysoGb3 was synthesized as previously described (12 ). The synthesis of [5,6,7,8,9] 13 C 5 -labeled lysoGb3 was accomplished as depicted in the scheme in the online Supplemental Data file. Key to the synthetic scheme was the preparation of [5,6,7,8,9]-13 C 5 -erythro-sphingosine 10, which was accomplished as follows (for full experimental and analytical details see the online Supplemental Data).…”

Section: Patient Samplesmentioning

confidence: 99%

“…Briefly, to 400 L of urine in an Eppendorf tube, 40 L of internal standard ( [5,6,7,8,9] 13 C 5 -labeled lysoGb3, 10 pmol/mL) was added and stirred briefly. Then, 960 L methanol and 500 L CHCl 3 were added with brief stirring.…”

Section: Extraction Of Lysogb3 From Urinementioning

confidence: 99%

“…Standard solutions of lysoGb3, [5,6,7,8,9] 13 C 5 -lysoGb3,and a mixture of both compounds were prepared with concentrations of 1 nmol/mL in 5 mmol/L ammonium formate/0.5% formic acid in methanol. The compounds were introduced in the mass spectrometer by direct infusion and the optimal tuning Quantification of Globotriaosylsphingosine conditions for both compounds in ES ϩ (electrospray positive) mode were determined, i.e., the signal response was optimized as a function of capillary and cone voltage and of flow and temperature of desolvation gas (nitrogen).…”

Section: Optimal Conditions For Lysogb3 Detection By Ms/msmentioning

confidence: 99%

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Quantification of Globotriaosylsphingosine in Plasma and Urine of Fabry Patients by Stable Isotope Ultraperformance Liquid Chromatography–Tandem Mass Spectrometry

Gold

Mirzaian²,

Dekker³

et al. 2013

Clinical Chemistry

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BACKGROUND Biochemical markers that accurately reflect the severity and progression of disease in patients with Fabry disease and their response to treatment are urgently needed. Globotriaosylsphingosine, also called lysoglobotriaosylceramide (lysoGb3), is a promising candidate biomarker. METHODS We synthesized lysoGb3 and isotope-labeled [5,6,7,8,9] 13C5-lysoGb3 (internal standard). After addition of the internal standard to 25 μL plasma or 400 μL urine from patients with Fabry disease and healthy controls, samples were extracted with organic solvents and the lysoGb3 concentration was quantified by UPLC-ESI-MS/MS (ultraperformance liquid chromatography–electrospray ionization–tandem mass spectrometry). Calibration curves were constructed with control plasma and urine supplemented with lysoGb3. In addition to lysoGb3, lyso-ene-Gb3 was quantified. Quantification was achieved by multiple reaction monitoring of the transitions m/z 786.4 > 282.3 [M+H]+ for lysoGb3, m/z 791.4 > 287.3 [M+H]+ for [5,6,7,8,9] 13C5-lysoGb3, and 784.4 > 280.3 [M+H]+ for lyso-ene-Gb3. RESULTS The mean (SD) plasma lysoGb3 concentration from 10 classically affected Fabry hemizygotes was 94.4 (25.8) pmol/mL (range 52.7–136.8 pmol/mL), from 10 classically affected Fabry heterozygotes 9.6 (5.8) pmol/mL (range 4.1–23.5 pmol/mL), and from 20 healthy controls 0.4 (0.1) pmol/mL (range 0.3–0.5 pmol/mL). Lyso-ene-Gb3 concentrations were 10%–25% of total lysoGb3. The urine concentration of lysoGb3 was 40–480 times lower than in corresponding plasma samples. Lyso-ene-Gb3 concentrations in urine were comparable or even higher than the corresponding lysoGb3 concentrations. CONCLUSIONS This assay for the quantification of lysoGb3 and lyso-ene-Gb3 in human plasma and urine samples will be an important tool in the diagnosis of Fabry disease and for monitoring the effect of enzyme replacement therapy in patients with Fabry disease.

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confidence: 99%

Section: Patient Samplesmentioning

confidence: 99%

Section: Extraction Of Lysogb3 From Urinementioning

confidence: 99%

Section: Optimal Conditions For Lysogb3 Detection By Ms/msmentioning

confidence: 99%

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Quantification of Globotriaosylsphingosine in Plasma and Urine of Fabry Patients by Stable Isotope Ultraperformance Liquid Chromatography–Tandem Mass Spectrometry

Gold

Mirzaian²,

Dekker³

et al. 2013

Clinical Chemistry

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show abstract

“…High plasma concentrations of lyso-Gb3 were observed in patients with this disease, 2 and these levels correlated with several of its manifestations 3 and decreased in response to enzyme-replacement therapy. 4,5 Furthermore, lysoGb3 promoted vascular smooth-muscle cell proliferation 2 as well as transforming growth factor-β1-mediated synthesis of extracellular matrix components in cultured podocytes at concentrations found in the plasma. 6 In Fabry's disease, vascular smooth-muscle cells and podocytes are cell targets, whereas fibrosis is a key feature of organ injury.…”

mentioning

confidence: 99%

The Human Plasma Lipidome

2012

N Engl J Med

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Pharmacological Chaperones as Potential Therapeutics for Lysosomal Storage Disorders: Preclinical Research to Clinical Studies

Boyd

Elias

et al. 2016

Lysosomes: Biology, Diseases, and Therapeutics

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Tissue and plasma globotriaosylsphingosine could be a biomarker for assessing enzyme replacement therapy for Fabry disease

Cited by 38 publications

References 22 publications

Quantification of Globotriaosylsphingosine in Plasma and Urine of Fabry Patients by Stable Isotope Ultraperformance Liquid Chromatography–Tandem Mass Spectrometry

Quantification of Globotriaosylsphingosine in Plasma and Urine of Fabry Patients by Stable Isotope Ultraperformance Liquid Chromatography–Tandem Mass Spectrometry

The Human Plasma Lipidome

Pharmacological Chaperones as Potential Therapeutics for Lysosomal Storage Disorders: Preclinical Research to Clinical Studies

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