Science Education

Unveiling Culprits, Part 1: The Immunological Morpheus

As medical research pushes back the veil on the causes of certain well-known diseases, we are sometimes surprised at the unlikely culprits. It sounds obvious today, for instance, that cigarette smoking can cause lung cancer: one can easily picture the smoke snaking down to the lungs and leaving a nasty deposit. Sometimes, however, the connection between the cause and the effect is far from intuitive.

Take narcolepsy, for example. Yes, narcolepsy.

It’s real.

Narcolepsy, which has a typical prevalence of 1 in every 2000 individuals, classically presents with excessive day-time sleepiness accompanied by sudden loss of muscle tone, sometimes in conjunction with hallucinations and a feeling of paralysis upon waking up or falling asleep1,2.

Want to know what it looks like to be narcoleptic? Here’s a short excerpt from an English programme:

It would be funny were it not real. Can you imagine going out shopping, applying for a job, attempting to drive a car, all the while knowing that, at any moment and in the blink of an eye, you could lose consciousness?

So what causes this bizarre disorder?

You may not have a medical degree, but I would invite you to make an educated guess. What could possibly cause an individual to experience erratic sleep patterns at night and a sudden onset of sleep during the day? You may think “brain”. You may think “genes”. But did you come up with “immune system”?

Our immune system is responsible for fighting off external threats—bacteria, viruses, parasitic worms—but, sometimes, it develops an affinity for part of us. This wrongful targeting of “self” molecules leads to an “autoimmune disease”, like rheumatoid arthritis in which inflammation occurs in the joints. As our portrait of narcolepsy becomes clearer, we are starting to believe it may very well be an autoimmune disease.

We have known for some time of a link between narcolepsy and specific mutations in genes belonging to the HLA family. These genes code for HLA proteins which play a crucial role in the identification of threats to the immune system. You can think of HLA proteins as a shopkeeper who grabs a thief’s collar and drags him to the nearest police station, asking for his arrest. If the shopkeeper grabs the wrong guy, justice will be ill-served; likewise, if the HLA proteins present the wrong molecule to a white blood cell, the immune system will mount an attack against the wrong foe.

Another piece of the puzzle was the gradual loss in narcoleptic individuals of a hormone either called hypocretin or orexin. This hormone inhibits Rapid-Eye-Movement (REM) sleep and helps keep us awake. But how are mutated HLA genes and a decrease in a sleep-associated hormone linked?

For many years, scientists have tried (and failed) to detect anti-hypocretin antibodies in the blood of narcoleptics; now, they seem to have isolated a type of white blood cell that targets hypocretin and that is only present in people who suffer from the sleep disorder3. This is the first direct evidence for narcolepsy being an autoimmune disease.

Some scientists are now hypothesizing that narcolepsy is triggered in individuals with predisposing mutations in certain genes, like HLA, when they encounter a molecule that is similar to the hormone hypocretin. This molecule may come in the form of a particular brand of flu vaccine, Pandemrix.

Wait a second, you say, a flu vaccine causes narcolepsy?! Ah ha! Didn’t you just write about how safe vaccines were and how we should all get vaccinated?

The answer (and it is not a simple one) in part 2.


(Feature picture by Dana7)


1. Scammell, T.E. (2013). Clinical features and diagnosis of narcolepsy. In: R. Benca (Ed.), UpToDate. Retrieved from

2. Hayley Willacy and Laurence Knott. “Narcolepsy and Cataplexy.” Accessed January 4, 2014.

3. De la Herrán-Arita AK, Kornum BR, Mahlios J, Jiang W, Lin L, Hou T, Macaubas C, Einen M, Plazzi G, Crowe C, Newell EW, Davis MM, Mellins ED, Mignot E. (2013). “CD4+ T Cell Autoimmunity to Hypocretin/Orexin and Cross-Reactivity to a 2009 H1N1 Influenza A Epitope in Narcolepsy.” Sci Transl Med. 5(216):216ra176. doi: 10.1126/scitranslmed.3007762. Abstract available here.


2 thoughts on “Unveiling Culprits, Part 1: The Immunological Morpheus

  1. Pingback: Unveiling Culprits, Part 2: The Hypnagogic Jab | Cracked Science

  2. Pingback: Replication Is Key: Revisting the Hypnagogic Jab | Cracked Science

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