Gaucher disease (GD) is a genetic disease with mutations in the GBA gene that encodes glucocerebrosidase causing complications such as anaemia and bone disease. GD is characterized by accumulation of the sphingolipids (SL) glucosylceramide (GL1), glucosylsphingosine (Lyso‐GL1), sphingosine (Sph) and sphingosine‐1‐phosphate (S1P). These SL are increased in the plasma of GD patients and the associated complications have been attributed to the accumulation of lipids in macrophages. Our recent findings indicated that red blood cells (RBCs) and erythroid progenitors may play an important role in GD pathophysiology. RBCs abnormalities and dyserythropoiesis have been observed in GD patients. Moreover, we showed higher SL levels in the plasma and in RBCs from untreated GD patients compared with controls. In this study, we quantified SL in 16 untreated GD patients and 15 patients treated with enzyme replacement therapy. Our results showed that the treatment significantly decreases SL levels in the plasma and RBCs. The increased SL content in RBCs correlates with abnormal RBC properties and with markers of disease activity. Because RBCs lack glucocerebrosidase activity, we investigated how lipid overload could occur in these cells. Our results suggested that SL overload in RBCs occurs both during erythropoiesis and during its circulation in the plasma.

中文翻译：

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鞘脂超载对戈谢病红细胞特性的影响。

戈谢病 (GD) 是一种在GBA 中发生突变的遗传性疾病编码葡萄糖脑苷脂酶的基因会导致贫血和骨病等并发症。GD 的特征是鞘脂 (SL) 葡萄糖神经酰胺 (GL1)、葡萄糖神经鞘氨醇 (Lyso-GL1)、鞘氨醇 (Sph) 和 1-磷酸鞘氨醇 (S1P) 的积累。这些 SL 在 GD 患者的血浆中增加，相关的并发症归因于巨噬细胞中脂质的积累。我们最近的研究结果表明，红细胞 (RBC) 和红细胞祖细胞可能在 GD 病理生理学中起重要作用。已在 GD 患者中观察到红细胞异常和红细胞生成异常。此外，与对照组相比，我们在未经治疗的 GD 患者的血浆和红细胞中显示出更高的 SL 水平。在这项研究中，我们量化了 16 名未经治疗的 GD 患者和 15 名接受酶替代疗法治疗的患者的 SL。我们的结果表明，治疗显着降低了血浆和红细胞中的 SL 水平。RBC 中 SL 含量的增加与异常 RBC 特性和疾病活动标志物相关。由于红细胞缺乏葡糖脑苷脂酶活性，我们研究了这些细胞中脂质超载是如何发生的。我们的结果表明，红细胞生成过程中及其在血浆中的循环过程中都会发生 SL 超载。