Clinical evaluation of chemokine and enzymatic biomarkers of Gaucher disease
Clinical evaluation of chemokine and enzymatic biomarkers of Gaucher disease
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DOI：
10.1016/j.bcmd.2005.05.005
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发表时间：
2005-09-01
影响因子：
2.3
通讯作者：
Cox, TM
中科院分区：
文献类型：
--
作者：
Deegan, PB;Moran, MT;Cox, TM
目的：高谢病是一种典型的孤儿疾病。用亚基葡萄糖酶进行酶替代疗法是有效的，但非常昂贵。为了更好地评估疾病的严重程度和对这种昂贵治疗的反应，我们评估了几种酶生物标志物和一种新描述的趋化因子。对象和方法：我们研究了48名未经治疗的成人I型高谢病：20名患者在引入酶替代治疗后进行了研究。通过连续测量血小板计数、磁共振成像内脏体积(脾和肝脏)、血清总酸性磷酸酶、血管紧张素转换酶(ACE)和溶酶体几丁质酶、几丁糖苷酶的活性来监测疾病活动性。用ELISA法检测血清中肺和活化调节趋化因子(PARC/CCL18)的含量。结果：高谢病患者血清PARC浓度是67例健康对照组的10~40倍，无重叠现象(P<；0.0001)。与壳三糖苷酶不同的是，PARC在所有个体中都能检测到。血清PARC是反映脾(R=0.53，P<0.01)、肝脏(R=0.65，P<0.01)体积和血小板计数(R=0.50，P<0.01)的可靠指标。在脾切除患者和壳三糖酶基因零等位基因患者中，血清PARC浓度与内脏体积和其他疾病活动性的生物标志物相关。与壳三糖苷酶不同，血清PARC浓度与脾和血小板对酶替代的反应性呈无偏相关的协变性。结论：血清PARC浓度与内脏高雪病和酶补充的关键临床反应相关。测定这种趋化因子是一种简便且普遍适用的方法，可以对高谢病患者的酶替代治疗进行客观监测。(C)2005年，爱思唯尔公司出版。
Purpose: Gaucher disease is an exemplary orphan disorder. Enzyme replacement therapy with imiglucerase is effective, but very expensive. To improve the assessment of severity of disease and responses to this costly treatment, we have evaluated several enzymatic biomarkers and a newly-described chemokine.Subjects and methods: We studied 48 untreated adults with Type I Gaucher disease: 20 patients were studied after the introduction of enzyme replacement. Disease activity was monitored by serial measurement of platelet count, visceral volumes (spleen and liver) by magnetic resonance imaging, serum activities of total acid phosphatase, angiotensin-converting enzyme (ACE) and the lysosomal chitinase, chitotriosidase. Pulmonary and activation-regulated chemokine (PARC/CCL 18) was also determined in serurn by ELISA.Results: Serum PARC concentrations were elevated 10-40-fold in patients with Gaucher disease compared with 67 healthy controls, without overlap (P < 0.0001). Unlike chitotriosidase, PARC was detectable in all individuals. Serum PARC was a reliable indicator of splenic (R = 0.53, P < 0.01) and liver (R = 0.65, P < 0.01) volume and platelet count (R = 0.50, P < 0.01). In splenectomized patients and in patients with null alleles of the chitotriosidase gene, serum PARC concentration correlates with visceral volume and other biomarkers of disease activity. Unlike chitotriosidase, serum PARC concentrations showed unbiased covariation with splenic and platelet responsiveness to enzyme replacement.Conclusion: Serum PARC concentrations are correlated with visceral Gaucher disease and with key clinical responses to enzyme complementation. Determination of this chemokine is a facile and universally applicable method that permits objective monitoring of enzyme replacement therapy for patients with Gaucher disease. (c) 2005 Published by Elsevier Inc.