Department of Pediatrics, National Gaucher Disease Treatment Center, Yale University School of Medicine, New Haven, CT 06562, USA.
J Inherit Metab Dis. 2011 Apr;34(2):429-37. doi: 10.1007/s10545-010-9271-7. Epub 2011 Feb 3.
Circulating biomarkers are important surrogates for monitoring disease activity in type I Gaucher disease (GD1). We and others have reported low high-density lipoprotein (HDL) in GD1. We assessed HDL cholesterol as a biomarker of GD1, with respect to its correlation with indicators of disease severity and its response to imiglucerase enzyme replacement therapy (ERT). In 278 consecutively evaluated GD1 patients, we correlated HDL cholesterol, chitotriosidase, and angiotensin-converting enzyme (ACE) with indicators of disease severity. Additionally, we measured the response of these biomarkers to ERT. HDL cholesterol was negatively correlated with spleen volume, liver volume, and GD severity score index; the magnitude of this association of disease severity with HDL cholesterol was similar to that for ACE and for chitotriosidase. Within individual patients monitored over many years, there was a strikingly strong correlation of HDL with liver and spleen volumes; there was a similarly strong correlation of chitotriosidase and ACE with disease severity in individual patients monitored serially over many years (chitotriosidase r = 0.96 to 0.98, ACE r = 0.88 to 0.94, and HDL r = -0.84 to -0.94, p < 0.001). ERT for 3 years resulted in a striking increase of HDL while serum levels of chitotriosidase and ACE decreased. Our results reveal markedly low HDL cholesterol in untreated GD1, a correlation with indicators of disease severity in GD1, and a rise towards normal after ERT. These findings suggest HDL cholesterol merits inclusion within the "biomarker basket" for monitoring of patients with GD1.
循环生物标志物是监测 1 型戈谢病（GD1）疾病活动的重要替代指标。我们和其他人已经报告了 GD1 中的低高密度脂蛋白（HDL）。我们评估了 HDL 胆固醇作为 GD1 的生物标志物，研究了其与疾病严重程度指标的相关性及其对伊米苷酶酶替代疗法（ERT）的反应。在 278 例连续评估的 GD1 患者中，我们将 HDL 胆固醇、壳三糖苷酶和血管紧张素转换酶（ACE）与疾病严重程度的指标相关联。此外，我们测量了这些生物标志物对 ERT 的反应。HDL 胆固醇与脾脏体积、肝脏体积和 GD 严重程度评分指数呈负相关；这种与 HDL 胆固醇相关的疾病严重程度的程度与 ACE 和壳三糖苷酶相似。在多年监测的个体患者中，HDL 与肝脏和脾脏体积之间存在惊人的强相关性；在多年监测的个体患者中，壳三糖苷酶和 ACE 与疾病严重程度之间也存在类似的强相关性（壳三糖苷酶 r = 0.96 至 0.98，ACE r = 0.88 至 0.94，HDL r = -0.84 至 -0.94，p < 0.001）。ERT 治疗 3 年后，HDL 显著升高，而血清壳三糖苷酶和 ACE 水平下降。我们的研究结果揭示了未经治疗的 GD1 中明显的低 HDL 胆固醇，与 GD1 中的疾病严重程度指标相关，ERT 后 HDL 胆固醇升高至正常水平。这些发现表明，HDL 胆固醇值得纳入 GD1 患者监测的“生物标志物篮子”。
