Autoimmunity to the Sodium-Level Sensor in the Brain Causes Essential Hypernatremia
Autoimmunity to the Sodium-Level Sensor in the Brain Causes Essential Hypernatremia
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DOI：
10.1016/j.neuron.2010.04.017
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发表时间：
2010-05-27
期刊：
影响因子：
16.2
通讯作者：
Noda, Masaharu
中科院分区：
文献类型：
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作者：
Hiyama, Takeshi Y.;Matsuda, Shinichi;Noda, Masaharu
Na-x是大脑中涉及钠稳态的体液钠水平传感器。Na-x基因敲除小鼠即使在脱水时也不会停止摄入盐。在此我们报告一个以原发性高钠血症为临床特徴但无明显下丘脑结构病变的病例，诊断为副肿瘤性神经系统疾病。患者有针对Na-x的自身抗体，沿着由强烈表达Na-x的Schwann样细胞组成的神经节细胞瘤。切除肿瘤并没有降低自身抗体水平或缓解症状。将患者血清中的免疫球蛋白组分静脉注射到小鼠体内，诱导水/盐摄入和利尿异常，导致高钠血症。在这些小鼠的脑中，观察到细胞死亡，同时沿着补体C3的局灶性沉积和Na-x特异性表达的脑室周围器官中的炎性浸润。因此，我们的研究结果提供了新的见解，高钠血症的发病机制有关的钠水平感应机制在人类。
Na-x is the sodium-level sensor of body fluids in the brain involved in sodium homeostasis. Na-x-knockout mice do not stop ingesting salt even when dehydrated. Here we report a case with clinical features of essential hypernatremia without demonstrable hypothalamic structural lesions, who was diagnosed as a paraneoplastic neurologic disorder. The patient had autoantibodies directed against Na-x, along with a ganglioneuroma composed of Schwann-like cells robustly expressing Na-x. The removal of the tumor did not reduce the autoantibody levels or relieve the symptoms. Intravenous injection of the immunoglobulin fraction of the patient's serum into mice induced abnormalities in water/salt intake and diuresis, which led to hypernatremia. In the brains of these mice, cell death was observed along with focal deposits of complement C3 and inflammatory infiltrates in circumventricular organs where Na-x is specifically expressed. Our findings thus provide new insights into the pathogenesis of hypernatremia relevant to the sodium-level-sensing mechanism in humans.