Narcolepsy patients have antibodies that stain distinct cell populations in rat brain and influence sleep patterns

• Narcolepsy is a chronic sleep disease with autoimmune origin. We explored occurrence of autoantibodies in narcolepsy and other sleep-related disorders (OSRDs) by screening human sera with immunohistochemistry on rat brains. Hypocretin/orexinergic neurons were not stained, but a prominent immunostaining pattern of hypothalamic melanin-concentrating hormone (MCH) and proopiomelanocortin (POMC) neurons was overrepresented in cases of narcolepsy and OSRD patients. The autoantigen was identified as the common C-terminal epitope of neuropeptide glutamic acid-isoleucine/α–melanocyte-stimulating hormone (NEI/αMSH). Purified IgGs from a patient with MCH/POMC staining injected intracerebroventricularly to rats caused disturbed sleep patterns. Also, GABAergic cortical interneurons were stained with other narcolepsy and OSRD sera. Thus, autoantibodies are frequent in patients with sleep disorders, and NEI/αMSH may be a previously unidentified autoantigen involved in pathomechanism(s). These findings indicate possible diagnostic/therapeutic targets.

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