Development and testing of new screening method for keratan sulfate in mucopolysaccharidosis IVA
Development and testing of new screening method for keratan sulfate in mucopolysaccharidosis IVA
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DOI：
10.1203/01.pdr.0000113767.60140.e9
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发表时间：
2004-04-01
影响因子：
3.6
通讯作者：
Noguchi, A
中科院分区：
文献类型：
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作者：
Tomatsu, S;Okamura, K;Noguchi, A
粘多糖样沉积症IVA（MPS IVA）是一种进行性溶酶体储存疾病，通过硫酸角质素（KS）过度储存导致骨骼发育不良。我们开发了一种使用KS特异性单克隆抗体的ELISA夹心法。分析了MPS IVA患者（年龄1-65岁）的45份血液和59份尿液标本，以确定KS浓度是否是早期诊断和疾病严重程度纵向评估的合适标志物。血液标本从表型严重（n = 36）和轻度（n = 9）的患者中获得。还分别分析了归类为重度（n = 56）和轻度（n = 12）患者的尿液标本。MPS IVA患者的血液KS水平（101-1525 ng/mL）比年龄匹配的对照组（15-323 ng/mL）高2 - 8倍。结果发现血KS水平随年龄和临床严重程度而变化。MPS IVA和对照组的血液KS水平在5 - 10岁之间达到峰值（平均值分别为776和234 ng/mL）。重度MPS IVA的血液水平是轻度MPS IVA的1.5倍。与血液相比，MPS IVA和对照组的尿KS水平在1至5岁之间达到峰值（15.3 vs 0.26 mg/g肌酐），此后随年龄增长而下降。尿KS水平也随年龄和临床严重程度而变化，重度MPS IVA表型与尿KS排泄量是轻度表型的6.7倍。这些发现表明，新的血液或尿液KS检测可能适用于MPS IVA的早期诊断和疾病严重程度的纵向评估。
Mucopolysaccharidosis IVA (MPS IVA), a progressive lysosomal storage disease, causes skeletal dysplasia through excessive storage of keratan sulfate (KS). We developed an ELISA-sandwich assay that used a MAb specific to KS. Forty-five blood and 59 urine specimens from MPS IVA patients (ages 1-65 y) were analyzed to determine whether KS concentration is a suitable marker for early diagnosis and longitudinal assessment of disease severity. Blood specimens were obtained from patients categorized as phenotypically severe (n = 36) and milder (n = 9). Urine specimens were also analyzed from patients categorized as severe (n = 56) and milder (n = 12), respectively. Blood KS levels (101-1525 ng/mL) in MPS IVA patients were two to eight times higher than those in age-matched controls (15-323 ng/mL). It was found that blood KS level varied with age and clinical severity. Blood KS levels in both MPS IVA and controls peaked between 5 and 10 y of age (mean, 776 versus 234 ng/mL, respectively). Blood levels in severe MPS IVA were 1.5 times higher than in the milder form. In contrast to blood, urine KS levels in both MPS IVA and controls peaked between I and 5 y (15.3 versus 0.26 mg/g creatinine), and thereafter declined with age. Urine KS level also varied with age and clinical severity, and the severe MPS IVA phenotype was associated with 6.7 times greater urine KS excretion than the milder one. These findings indicate that the new assay for blood or urine KS may be suitable for early diagnosis and longitudinal assessment of disease severity in MPS IVA.