The Autoimmunity Hypothesis in Narcolepsy

Since the finding in 1983 that narcolepsy-cataplexy has a strong genetic association with a particular HLA class II haplotype, it has been hypothesized that most sporadic cases result from autoimmunity. Recent evidence indicates that the disease results from the death of the small number of hypocretin (hcrt)-producing cells in the lateral hypothalamus, strongly suggesting that an autoimmune attack against these cells is the most common cause of narcolepsy. We propose to validate this widelyheld view with experimental evidence that will suggest potential autoantigens, provide an autoimmune mouse model, and show direct evidence of autoimmunity in narcoleptic patients.