Abstract：
Gaucher disease (GD) has a high carrier rate among Ashkenazi Jews.The most common disease-causing variant in this population N370S, is also prevalent pan-ethnically. This has led to speculations of some protective effect for carriers of this variant. During the recent COVID-19 pandemic, GD patients reportedly had a surprisingly low infection rate and mild symptoms considering their disease status. As SARS-CoV-2 gains entry into the cell via membrane-bound angiotensin-converting enzyme 2 (ACE2), we speculated that differences in levels of soluble ACE2 in GD patients could contribute to this protective state. While ACE is known to be elevated in GD, to our knowledge, ACE2 levels have not been explored. We measured serum and macrophage-bound levels of ACE and ACE2 by ELISA and western blot, respectively, in GD patients and age- and sex-matched controls. Our results reveal a significant elevation of both serum and macrophage-bound ACE and ACE2 in GD patients compared to healthy controls. This elevation appears to be mitigated by GD treatment. Moreover, the most robust ACE2 elevation was observed in N370S homozygotes, and was not effected by treatment. Since coronaviruses use the ACE2 receptor as a gateway for host cell entry, we speculate that elevated circulating ACE2 may serve as a decoy. This might explain the observed mild infections in GD patients during the COVID-19 pandemic.
摘要：
戈谢病（GD）在德系犹太人中具有很高的携带率。该人群中最常见的致病变异N370S，泛种族也很普遍。这导致了对该变体的携带者的一些保护作用的推测。在最近的COVID-19大流行期间，据报道,考虑到他们的疾病状态,GD患者具有令人惊讶的低感染率和轻度症状。当SARS-CoV-2通过膜结合血管紧张素转换酶2（ACE2）进入细胞时，我们推测GD患者中可溶性ACE2水平的差异可能导致这种保护状态.虽然已知ACE在GD中升高，根据我们的知识，尚未探索ACE2水平。我们通过ELISA和Westernblot检测血清和巨噬细胞结合的ACE和ACE2水平。分别,GD患者和年龄和性别匹配的对照。我们的结果表明，与健康对照组相比，GD患者的血清和巨噬细胞结合的ACE和ACE2均显着升高。GD治疗似乎减轻了这种升高。此外，在N370S纯合子中观察到最强烈的ACE2升高，并没有受到治疗的影响。由于冠状病毒使用ACE2受体作为进入宿主细胞的通道，我们推测循环ACE2升高可能是一种诱饵.这可能解释了在COVID-19大流行期间观察到的GD患者轻度感染。
