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A convenient approach to facilitate monitoring Gaucher disease progression and therapeutic response
Analyst ( IF 4.2 ) Pub Date : 2017-07-21 00:00:00 , DOI: 10.1039/c7an00938k
Wujuan Zhang 1, 2, 3, 4 , Melissa Oehrle 1, 2, 3, 4 , Carlos E. Prada 2, 3, 4, 5, 6 , Ida Vanessa D. Schwartz 7, 8, 9, 10, 11 , Somchai Chutipongtanate 12, 13, 14, 15 , Duangrurdee Wattanasirichaigoon 12, 13, 14, 15 , Venette Inskeep 2, 3, 4, 5 , Mei Dai 2, 3, 4, 16 , Dao Pan 2, 3, 4, 16 , Ying Sun 2, 3, 4, 5 , Kenneth D. R. Setchell 1, 2, 3, 4
Affiliation  

Gaucher disease (GD) is caused by mutations on the GBA1 gene leading to deficiency in acid β-glucosidase (GCase) and subsequent accumulation of its substrates, glucosylceramide (GlcC) and glucosylsphingosine (GlcS). GlcS in plasma has been proposed as a highly sensitive and specific biomarker for the diagnosis of GD and for monitoring disease progression and response to therapy. Here we report a novel robust and accurate hydrophilic interaction liquid chromatography tandem mass spectrometric method (HILIC-MS/MS) for the direct measurement of glucosylsphingosine (GlcS) in dried plasma spots (DPS). The method was also capable of resolving the isomeric pair, glucosylsphingosine and galactosylsphingosine, the latter of which was proposed as a promising biomarker for Krabbe disease. The method was fully validated and applied to the analysis of 19 GD patients and carriers. The GlcS levels in 9 GD type I patients who have been on enzyme replacement therapy (ERT) were reduced to a mean of 31.0 nM, much lower compared to a pre-treated specimen at a level of 85.8 nM, but still significantly elevated compared to healthy controls. GlcS concentrations in three treated type III GD patients were much lower compared to an untreated patient. In our preclinical GD studies, 4L;C* mice (subacute nGD model) exhibited comparable levels of plasma GlcS, but had much higher GlcS accumulation in the brain than those of 9V/null mice (chronic neuropathic GD model). Our method for the measurement of GlcS in DPS proved to be a very convenient approach for sample collection, storage and shipping nationwide and internationally.

中文翻译:

一种方便的方法来促进监测Gaucher疾病的进展和治疗反应

高歇病(GD)是由GBA1上的突变引起的导致酸性β-葡萄糖苷酶(GCase)缺乏并随后积累其底物,葡萄糖基神经酰胺(GlcC)和葡萄糖基鞘氨醇(GlcS)的基因。血浆中的GlcS已被提出作为GD的诊断和监测疾病进展以及对治疗的反应的高度敏感和特异的生物标记。在这里,我们报告了一种新型的稳健而准确的亲水相互作用液相色谱串联质谱法(HILIC-MS / MS),用于直接测量干燥血浆斑点(DPS)中的葡萄糖基鞘氨醇(GlcS)。该方法还能够解析异构对,即葡糖基鞘氨醇和半乳糖基鞘氨醇,其中后者被建议作为克拉伯病的有前途的生物标志物。该方法经过充分验证,可用于19例GD患者和携带者的分析。接受酶替代治疗(ERT)的9例GD I型患者中的GlcS水平平均降低至31.0 nM,与85.8 nM的预处理标本相比要低得多,但与健康对照。与未经治疗的患者相比,三名经治疗的III型GD患者的GlcS浓度要低得多。在我们的临床前GD研究中,4L; C *小鼠(亚急性nGD模型)表现出相当水平的血浆GlcS,但与9V / null小鼠(慢性神经病GD模型)相比,其在大脑中的GlcS积聚要高得多。实践证明,我们的DPS中GlcS的测量方法是在全国和国际范围内进行样品收集,存储和运输的非常便捷的方法。与85.8 nM的预处理标本相比,它要低得多,但与健康对照相比仍显着升高。与未经治疗的患者相比,三名经治疗的III型GD患者的GlcS浓度要低得多。在我们的临床前GD研究中,4L; C *小鼠(亚急性nGD模型)表现出相当水平的血浆GlcS,但与9V / null小鼠(慢性神经病GD模型)相比,其在大脑中的GlcS积聚要高得多。实践证明,我们的DPS中GlcS的测量方法是在全国和国际范围内进行样品收集,存储和运输的非常便捷的方法。与85.8 nM的预处理标本相比,它要低得多,但与健康对照相比仍显着升高。与未经治疗的患者相比,三名经治疗的III型GD患者的GlcS浓度要低得多。在我们的临床前GD研究中,4L; C *小鼠(亚急性nGD模型)表现出相当水平的血浆GlcS,但与9V / null小鼠(慢性神经病GD模型)相比,其在大脑中的GlcS积聚要高得多。实践证明,我们的DPS中GlcS的测量方法是在全国和国际范围内进行样品收集,存储和运输的非常便捷的方法。在我们的临床前GD研究中,4L; C *小鼠(亚急性nGD模型)表现出相当水平的血浆GlcS,但与9V / null小鼠(慢性神经病GD模型)相比,其在大脑中的GlcS积聚要高得多。实践证明,我们的DPS中GlcS的测量方法是在全国和国际范围内进行样品收集,存储和运输的非常便捷的方法。在我们的临床前GD研究中,4L; C *小鼠(亚急性nGD模型)表现出相当水平的血浆GlcS,但与9V / null小鼠(慢性神经病GD模型)相比,其在大脑中的GlcS积聚要高得多。实践证明,我们的DPS中GlcS的测量方法是在全国和国际范围内进行样品收集,存储和运输的非常便捷的方法。
更新日期:2017-09-08
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