Detection of autoantibodies against hypocretin, hcrtr1, and hcrtr2 in narcolepsy: Anti-hcrt system antibody in narcolepsy
Detection of autoantibodies against hypocretin, hcrtr1, and hcrtr2 in narcolepsy: Anti-hcrt system antibody in narcolepsy
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DOI：
10.1093/sleep/29.5.633
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发表时间：
2006-05-01
期刊：
影响因子：
5.6
通讯作者：
Honda, Makoto
中科院分区：
文献类型：
--
作者：
Tanaka, Susumu;Honda, Yutaka;Honda, Makoto
研究目的：下丘脑神经传递系统受损被认为在发作性睡病的病理生理学中起重要作用。基于自身免疫异常与人类白细胞抗原-DR131*1501/DQ1311*0602密切相关，推测自身免疫异常是发作性睡病的病因。目前尚不清楚抗下丘脑角蛋白受体自身抗体(hcrtr1和hcrtr2)是否与发作性睡病有关。设计：我们开发了一种新的放射配基结合分析来解决这个问题。收集181例发作性睡病患者、10例其他睡眠过度患者和91例正常对照的血清。通过体外转录/翻译系统合成了人[S-35]-hcrt、hcrtr1和hcrtr2。用放射配基结合法检测自身抗体和各蛋白的免疫复合物。结果：3例患者中检出抗下丘脑皮质激素受体抗体，1例患者检测到hcrtr1抗体，5例患者检测到hcrtr2抗体。对照组中2例hcrtr1阳性，1例hcrtr2阳性。未发现这些自身抗体与HLADRB1*1501/DQB1*0602单倍型、猝倒的存在、主观夜间睡眠障碍的存在或Epworth嗜睡量表的评分之间的关系。结论：尽管我们检测到了针对下丘脑神经传递系统的自身抗体，但我们的结果并不支持以下述自身抗体介导的下丘脑系统功能障碍是发作性睡病的病理生理学基础的假设。
Study Objectives: The impairment of hypocretin neurotransmission system is considered to play a major role in the pathophysiology of narcolepsy. It has been hypothesized that autoimmune abnormalities underlie the etiology of narcolepsy, based on the tight association with HLA-DR131*1501/DQ1311*0602. It remains unclear if autoantibodies against hypocretin receptors (hcrtr1 and hcrtr2) are involved in narcolepsy.Design: We have developed a novel radioligand binding assay to address this question. Sera from 181 patients with narcolepsy, 10 patients with other hypersomnias, and 91 control subjects were used. Human [S-35]-Hcrt, hcrtr1, and hcrtr2 were synthesized by in vitro transcription/translation system. The immune complex of autoantibody and each [S-35]-protein were immunoprecipitated and quantified using a radioligand-binding assay.Results: We detected autoantibodies against hypocretin in 3 patients, hcrtr1 in 1 patient, and hcrtr2 in 5 patients with narcolepsy. Positive reactions were also found against hcrtr1 in 2 and hcrtr2 in I control subjects. No relationships were found between these autoantibodies and HLADRB1*1501/DQB1*0602 haplotypes, presence of cataplexy, presence of subjective nocturnal sleep disruption, or the score on the Epworth Sleepiness Scale.Conclusions: Although we have detected autoantibodies against the hypocretin neurotransmission system, our results do not support the hypothesis that autoantibody-mediated dysfunction in the hypocretin system underlies the pathophysiology of narcolepsy.