NEJM：多发性硬化症诊断新标记物

即使是有丰富经验的神经学家，诊断多发性硬化症（MS）也是一项巨大挑战。这种自身免疫性疾病有许多症状，但很少会出现一个统一的临床表现。现在MS中有关免疫反应的新研究发现可能有助于改善这种疾病的诊断。科学家分析MS患者的血液，发现一种攻击细胞膜上特定钾离子通道的抗体。钾离子通道在肌肉和神经细胞传送脉冲过程中发挥了重要作用，而正是上述这些传输过程在MS患者体内受到了抑制。
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研究结果发表在最近一期​​<em>New England Journal of Medicine</em>杂志。

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慕尼黑工业大学Klinikum rechts der Isar医院神经内科教授Bernhard Hemmer解释说：我们发现几乎一半的多发性硬化症患者体内都存在这种抗体。而这一新生物标志物是不存在于健康人体内。因此，这一发现可能表明钾通道KIR4.1是MS自身免疫反应的靶标之一。没有KIR4.1通道的人类和动物神经系统会发生故障，不能妥善协调自身行动。

存在于神经胶质细胞膜上的KIR4.1是主要负责控制大脑的新陈代谢和形成髓鞘。神经学家将进行后续研究探讨KIR4.1抗体是如何影响MS的发生发展。这种抗体在其他神经系统疾病的人中极为罕见，使得它在未来可能是一个重要的潜在MS诊断标志物。
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<a title="" href="http://dx.doi.org/10.1056/NEJMoa1110740" target="_blank">doi:10.1056/NEJMoa1110740</a>
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<br/><strong>Potassium Channel KIR4.1 as an Immune Target in Multiple Sclerosis
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Rajneesh Srivastava, Muhammad Aslam, Sudhakar Reddy Kalluri, Lucas Schirmer, Dorothea Buck, Bj?rn Tackenberg, Veit Rothhammer, Andrew Chan, Ralf Gold, Achim Berthele, Jeffrey L. Bennett, Thomas Korn, Bernhard Hemmer.

<br/><strong>Background</strong><br/>

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Many findings suggest that the disease has an autoimmune pathogenesis; the target of the immune response is not yet known.
<br/><strong>Methods</strong><br/>

We screened serum IgG from persons with multiple sclerosis to identify antibodies that are capable of binding to brain tissue and observed specific binding of IgG to glial cells in a subgroup of patients. Using a proteomic approach focusing on membrane proteins, we identified the ATP-sensitive inward rectifying potassium channel KIR4.1 as the target of the IgG antibodies. We used a multifaceted validation strategy to confirm KIR4.1 as a target of the autoantibody response in multiple sclerosis and to show its potential pathogenicity in vivo.
<br/><strong>Results</strong><br/>

Serum levels of antibodies to KIR4.1 were higher in persons with multiple sclerosis than in persons with other neurologic diseases and healthy donors (P&lt;0.001 for both comparisons). We replicated this finding in two independent groups of persons with multiple sclerosis or other neurologic diseases (P&lt;0.001 for both comparisons). Analysis of the combined data sets indicated the presence of serum antibodies to KIR4.1 in 186 of 397 persons with multiple sclerosis (46.9%), in 3 of 329 persons with other neurologic diseases (0.9%), and in none of the 59 healthy donors. These antibodies bound to the first extracellular loop of KIR4.1. Injection of KIR4.1 serum IgG into the cisternae magnae of mice led to a profound loss of KIR4.1 expression, altered expression of glial fibrillary acidic protein in astrocytes, and activation of the complement cascade at sites of KIR4.1 expression in the cerebellum.
<br/><strong>Conclusions</strong><br/>

KIR4.1 is a target of the autoantibody response in a subgroup of persons with multiple sclerosis. (Funded by the German Ministry for Education and Research and Deutsche Forschungsgemeinschaft.)

<br/>来源：生物谷

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