Increased immune complexes of hypocretin autoantibodies in narcolepsy.
Increased immune complexes of hypocretin autoantibodies in narcolepsy.
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DOI：
10.1371/journal.pone.0013320
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发表时间：
2010-10-13
期刊：
影响因子：
3.7
通讯作者：
Dauvilliers Y
中科院分区：
文献类型：
--
作者：
Deloumeau A;Bayard S;Coquerel Q;Déchelotte P;Bole-Feysot C;Carlander B;Cochen De Cock V;Fetissov SO;Dauvilliers Y
下丘脑泌素肽参与睡眠-觉醒周期的调节，而下丘脑泌素信号转导的缺陷和下丘脑泌素神经元的缺失是发作性睡病-惊厥的原因。然而，下丘脑泌素系统在发作性睡病-紧张症中改变的机制及其与其他中枢性睡眠过度的相关性仍然未知。在这里，我们研究了中枢性睡眠过度是否与下丘脑泌素-1肽作为免疫复合物反应的自身抗体有关。通过酶联免疫吸附试验测定与下丘脑泌素-1肽反应的游离和解离（总）自身抗体的血清水平，并分析82例发作性睡病-痉挛、发作性睡病无痉挛或特发性嗜睡受试者的临床参数，并与25例健康对照组进行比较。发作性睡病-紧张症患者血清中抗下丘脑泌素-1的总IgG自身抗体水平升高，而非游离IgG自身抗体。在所有患者组中发现针对下丘脑泌素-1的复合IgG自身抗体水平增加，发作性睡病-紧张症进一步增加。总IgM下丘脑泌素-1自身抗体的水平也升高，在所有组的患者。在所有三组患者中，均发现与从发作性睡病-痉挛受试者血清中纯化的下丘脑泌素-1 IgG自身抗体亲和力反应的抗独特型IgM自身抗体水平升高。病程与血清下丘脑泌素-1 IgG和IgM自身抗体和抗独特型IgM自身抗体水平呈负相关。中枢性睡眠过度，特别是发作性睡病-昏厥的特征在于针对下丘脑泌素-1的自身抗体的较高血清水平，其作为免疫复合物存在，最有可能与抗独特型自身抗体一起存在，表明其与睡眠-觉醒周期调节机制相关。
Hypocretin peptides participate in the regulation of sleep-wake cycle while deficiency in hypocretin signaling and loss of hypocretin neurons are causative for narcolepsy-cataplexy. However, the mechanism responsible for alteration of the hypocretin system in narcolepsy-cataplexy and its relevance to other central hypersomnias remain unknown. Here we studied whether central hypersomnias can be associated with autoantibodies reacting with hypocretin-1 peptide present as immune complexes. Serum levels of free and dissociated (total) autoantibodies reacting with hypocretin-1 peptide were measured by enzyme-linked immunosorbent assay and analyzed with regard to clinical parameters in 82 subjects with narcolepsy-cataplexy, narcolepsy without cataplexy or idiopathic hypersomnia and were compared to 25 healthy controls. Serum levels of total but not free IgG autoantibodies against hypocretin-1 were increased in narcolepsy-cataplexy. Increased levels of complexed IgG autoantibodies against hypocretin-1 were found in all patients groups with a further increase in narcolepsy-cataplexy. Levels of total IgM hypocretin-1 autoantibodies were also elevated in all groups of patients. Increased levels of anti-idiotypic IgM autoantibodies reacting with hypocretin-1 IgG autoantibodies affinity purified from sera of subjects with narcolepsy-cataplexy were found in all three groups of patients. Disease duration correlated negatively with serum levels of hypocretin-1 IgG and IgM autoantibodies and with anti-idiotypic IgM autoantibodies. Central hypersomnias and particularly narcolepsy-cataplexy are characterized by higher serum levels of autoantibodies directed against hypocretin-1 which are present as immune complexes most likely with anti-idiotypic autoantibodies suggesting their relevance to the mechanism of sleep-wake cycle regulation.
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