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Sleep. 2006 May;29(5):633-8.

Detection of autoantibodies against hypocretin, hcrtrl, and hcrtr2 in narcolepsy: anti-Hcrt system antibody in narcolepsy.

Author information

1
The Sleep Disorders Project, Department of Sleep Disorders Research, Tokyo Institute of Psychiatry, Setagaya-ku, Tokyo, Japan. stanaka@prit.go.jp

Abstract

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-DRB1*1501/ DQB1*0602. It remains unclear if autoantibodies against hypocretin receptors (hcrtrl 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 [35S]-Hcrt, hcrtrl, and hcrtr2 were synthesized by in vitro transcription/translation system. The immune complex of autoantibody and each [35S]-protein were immunoprecipitated and quantified using a radioligand-binding assay.

RESULTS:

We detected autoantibodies against hypocretin in 3 patients, hcrtrl in 1 patient, and hcrtr2 in 5 patients with narcolepsy. Positive reactions were also found against hcrtrl in 2 and hcrtr2 in 1 control subjects. No relationships were found between these autoantibodies and HLA-DRB1*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.

PMID:
16774153
[Indexed for MEDLINE]

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