The levels of urinary glycosaminoglycans of patients with attenuated and severe type of mucopolysaccharidosis II determined by liquid chromatography-tandem mass spectrometry.
The levels of urinary glycosaminoglycans of patients with attenuated and severe type of mucopolysaccharidosis II determined by liquid chromatography-tandem mass spectrometry.
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DOI：
10.1016/j.ymgmr.2016.03.009
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发表时间：
2016-06
影响因子：
1.9
通讯作者：
Okuyama T
中科院分区：
文献类型：
--
作者：
Mashima R;Sakai E;Tanaka M;Kosuga M;Okuyama T
糖胺聚糖（GAGs）在调节细胞外信号、神经元发育和软骨维持中发挥重要作用。细胞外总gag浓度已被用作诊断粘多糖病（mps）的既定措施。已知在与MPS相关的病理条件下，GAGs中硫酸肝素（HS）、硫酸皮肤素（DS）和硫酸软骨素升高。此外，其中一种或几种疾病特异性的选择性积累也被用于MPS亚型的估计。一种先前开发的方法[Auray-Blais C et al.]分子遗传与代谢[j](2011): 49-56。采用液相色谱串联质谱法（LC-MS/MS）测量GAGs浓度，精度更高。为了了解MPS II患者尿液中HS和DS的选择性积累是否能区分MPS II的减毒型和重症型，我们用这种方法检测了HS和DS的浓度。与健康对照相比，我们发现所有MPS ii型患者HS和DS明显升高。在确认抗体滴度升高接受ERT治疗的患者中，减毒型患者尿HS浓度低于严重型MPS II患者。在这些患者中，LC-MS/MS测定的DS浓度和DMB测定的总GAG浓度不依赖于抗体的积累。这些结果表明，本研究采用的LC-MS/MS方法可以区分不同临床背景的MPS II亚型。
Glycosaminoglycans (GAGs) play important roles on the regulation of extracellular signaling, neuronal development, and cartilage maintenance. The extracellular concentration of total GAGs has been used as an established measure for the diagnosis of mucopolysaccharidoses (MPSs). Heparan sulfate (HS), Dermatan sulfate (DS) and chondroitin sulfate are known to be elevated in the GAGs under pathological conditions associated with MPS. Furthermore, the selective accumulation of disease-specific one of, or a combination of, them has also been used for the estimation of subtypes of MPS. A previously developed method [Auray-Blais C et al. Molecular Genetics and Metabolism 102 (2011) 49–56.] measures the concentration of GAGs using liquid chromatography with tandem mass spectrometry (LC-MS/MS) with higher precision. To ask whether the selective accumulation of HS and DS in the urine of MPS II patients discriminate the attenuated and severe type of MPS II, we examined the concentrations of HS and DS by this methodology. Compared to the healthy controls, we found a marked elevation of HS and DS in all of the MPS II-affected patients. Among patients who received ERT with confirmed elevation of antibody titer, the concentrations of HS in the urine of patients with attenuated type were lower than those with severe type of MPS II. In these patients, the concentrations of DS by LC-MS/MS and of total GAG by DMB failed to depend on the accumulation of antibody. These results suggest that the LC-MS/MS method employed in this study might discriminate the subtypes of MPS II in different clinical background.