Boot Rolf G, Verhoek Marri, Langeveld Mirjam, Renkema G Herma, Hollak Carla E M, Weening Jan J, Donker-Koopman Wilma E, Groener Johanna E, Aerts Johannes M F G
Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
J Inherit Metab Dis. 2006 Aug;29(4):564-71. doi: 10.1007/s10545-006-0318-8. Epub 2006 May 30.
Glucosylceramide-laden tissue macrophages in Gaucher patients secrete large quantities of chitotriosidase and CC chemokine ligand 18 (CCL18), resulting in markedly increased plasma levels. We have comparatively investigated the occurrence of both parameters in plasma and urine samples of Gaucher patients. Chitotriosidase was high in urine samples of some symptomatic patients, but elevations did not correlate with increased plasma concentrations. Urinary chitotriosidase was particularly high in a patient with severe kidney involvement and local storage cell infiltration. Urinary levels of CCL18 were also highly elevated in samples from Gaucher patients as compared to controls. The median value of the CCL18/creatinine ratio in urine samples of 31 Gaucher patients was 143.3 pg/micromol (range 32-551) and in those of 12 normal subjects was 4.1 pg/micromol (range 1.3-6.8). In sharp contrast to chitotriosidase, increases in the low-molecular-mass chemokine CCL18 in urine and plasma specimens of Gaucher patients correlated well. A correlation was also observed for reductions in urinary and plasma CCL18 following therapy. It is concluded that assessment of urinary CCL18 of Gaucher patients gives insight into the total body burden on Gaucher cells, whereas that of chitotriosidase does not. Urinary chitotriosidase appears rather to be a reflection of renal pathology.
戈谢病患者中富含葡糖神经酰胺的组织巨噬细胞会分泌大量的壳三糖苷酶和CC趋化因子配体18（CCL18），导致血浆水平显著升高。我们比较研究了戈谢病患者血浆和尿液样本中这两个参数的情况。一些有症状患者的尿液样本中壳三糖苷酶水平较高，但升高情况与血浆浓度增加无关。在一名有严重肾脏受累和局部贮积细胞浸润的患者中，尿壳三糖苷酶特别高。与对照组相比，戈谢病患者样本中CCL18的尿液水平也显著升高。31名戈谢病患者尿液样本中CCL18/肌酐比值的中位数为143.3 pg/微摩尔（范围32 - 551），12名正常受试者的该比值中位数为4.1 pg/微摩尔（范围1.3 - 6.8）。与壳三糖苷酶形成鲜明对比的是，戈谢病患者尿液和血浆样本中低分子量趋化因子CCL18的增加情况相关性良好。治疗后尿液和血浆中CCL18的降低情况也存在相关性。得出的结论是，评估戈谢病患者的尿液CCL18可深入了解戈谢细胞的全身负荷情况，而壳三糖苷酶则不能。尿壳三糖苷酶似乎更反映肾脏病理情况。
