Is Narcolepsy an Auto-Immune Disease?

In the prestigious journal Nature, there is an article detailing investigation into whether narcolepsy could be auto-immune (1) .

There has been prior evidence that points to it being an autoimmune disease, but this is the first direct evidence that it is. Researchers found that all of the study patients with narcolepsy had T-Cells (specialized white blood cells of the immune system) in their blood that recognized (significantly reacted to) fragments of the hypocretin molecule.  The control patients that did not have narcolepsy, did not have T Cells that responded significantly to these protein fragments.  The patients with narcolepsy had a 10-times higher number of  reactive immune T cells vs the non-narcolepsy controls.

The study raises still more questions, with the details of how the hypocretin protein fragments are processed by the immune cells, since several types of immune cells are involved, and what role this may play in the destruction of the hypocretin-producing nerve cells (perhaps it is instead a result of destruction of those cells).

The life-long neurological sleep disorder called Narcolepsy affects about 1 person in 1200, usually beginning in adolescence or early adulthood, with symptoms including excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. It is due to a deficiency of a brain hormone called “hypocretin” (aka orexin), which is normally produced by a small grouping of special brain cells located in the hypothalamus. These cells die off, and therefore don’t secrete the hypocretin.  Tests to diagnose Narcolepsy include Sleep Studies and measuring levels of Hypocretin in spinal fluid (from a spinal tap procedure).

(1) [Nature volume 562, pages 63–68 (2018)]


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Dr. Pamela Peak

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