Glucosylsphingosine is a key biomarker of Gaucher disease.
Glucosylsphingosine is a key biomarker of Gaucher disease.
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DOI：
10.1002/ajh.24491
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发表时间：
2016-11
影响因子：
12.8
通讯作者：
Mistry PK
中科院分区：
文献类型：
--
作者：
Murugesan V;Chuang WL;Liu J;Lischuk A;Kacena K;Lin H;Pastores GM;Yang R;Keutzer J;Zhang K;Mistry PK
戈谢病（GD）导致葡萄糖神经酰胺（GL 1）及其脱酰基溶血脂、葡萄糖鞘氨醇（lyso-GL 1）的积累，这与介导免疫失调和骨骼疾病有关。我们研究的目的是评估血浆Lyso-GL 1作为GD的生物标志物及其对治疗的反应。采用LC-MS/MS法测定169例GD 1型患者血浆溶血-GL 1水平，并采用Pearson相关系数、Wilcoxon Mann Whitney检验和多元线性回归分析其显著性预测因素。使用倾向评分匹配患者的治疗模式：酶替代疗法（ERT）与酒石酸依格鲁司他SRT（ELI-SRT）。健康对照中的Lyso-GL 1水平平均为1.5 ng/ml（1.3 - 1.7; 95% CI）。在未经治疗的GD患者中，水平显著升高（180.9 ng/ml：95% CI，145.4 - 216.5），ERT导致显著降低（89 ng/ml：95% CI，69.2 - 129.4）（p<0.001）。Lyso-GL 1与壳三糖苷酶（r=0.59 p<0.001）、CCL 18（r= 0.62 p <0.001）、肝肿大（r=0.28 p<0.001）、脾肿大（r=0.27 p=0.003）、脾切除术（p=0.01）和治疗模式（p<0.001）相关。通过多元线性回归，溶血-GL 1的最强预测因子是年龄（p<0.001）、脾切除术（p=0.02）、壳三糖苷酶（p<0.001）和CCL 18水平（p=0.001）。在倾向评分匹配以获得接受ERT与ELI-SRT的可比患者组后，接受ELI-SRT的患者中溶血-GL 1水平低113 ng/ml（95% CI：136 - 90.3 ng/ml p<0.001）。血浆lyso-GL 1是GD的关键生物标志物。ERT降低了lyso-GL 1水平。通过倾向性评分，ELI-SRT导致溶血-GL 1的降低幅度大于ERT。
Gaucher disease (GD) leads to accumulation of glucosylceramide (GL1) and its deacylated lysolipid, glucosylsphingosine (lyso-GL1) which is implicated in mediating immune dysregulation and skeletal disease. The aim of our study was to assess plasma Lyso-GL1 as a biomarker of GD and its response to therapy. Plasma lyso-GL1 in 169 patients with GD type 1 (GD1) was measured by LC-MS/MS. Significant predictors of were assessed by Pearson’s correlation coefficient, Wilcoxon Mann Whitney test and multiple linear regression. Propensity scores were used to match patients on treatment mode: Enzyme Replacement Therapy (ERT) vs Eliglustat Tartrate SRT (ELI-SRT). Lyso-GL1 levels in healthy controls on average was 1.5 ng/ml (1.3 – 1.7; 95% CI). In untreated GD patients, the levels were massively elevated (180.9 ng/ml: 95% CI, 145.4 – 216.5) and ERT resulted in marked reduction (89 ng/ml: 95% CI, 69.2 – 129.4) (p<0.001). Lyso-GL1 correlated with chitotriosidase (r=0.59 p<0.001), CCL18 (r= 0.62 p <0.001), hepatomegaly (r=0.28 p<0.001), splenomegaly (r=0.27 p=0.003), splenectomy (p=0.01) and treatment mode (p<0.001). By multiple linear regression, the strongest predictors of lyso-GL1 were age (p<0.001), splenectomy (p=0.02), Chitotriosidase (p<0.001) and CCL18 levels (p=0.001). After propensity score matching to obtain comparable groups of patients on ERT vs ELI-SRT, lyso-GL1 levels were lower among patients receiving ELI-SRT by 113 ng/ml (95% CI: 136 – 90.3 ng/ml p<0.001). Plasma lyso-GL1 is a key biomarker of GD. ERT reduced lyso-GL1 levels. By propensity scoring, ELI-SRT resulted in greater reduction of lyso-GL1 than ERT.