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New Study Sheds Light on Autoimmune Nature of Narcolepsy

Posted on September 20, 2021
Medically reviewed by
Allen J. Blaivas, D.O.
Article written by
Brooke Dulka, Ph.D.

Narcolepsy is a chronic sleep disorder that is characterized by symptoms such as excessive daytime sleepiness, sleep attacks, cataplexy (sudden muscle weakness), sleep paralysis, and dream-like hallucinations. It may also be an autoimmune disease. The causes of narcolepsy are primarily biological, but the environment also plays a role. In fact, according to new research, some environmental factors may play a larger role than previously thought. Specifically, the H1N1 flu virus may be a contributor to the pathogenesis (development) of narcolepsy.

The Pandemrix Vaccine

During the 2009 swine flu pandemic, several European countries distributed the Pandemrix vaccine, a vaccine for the H1N1 virus, to their populations. Shortly afterward, researchers discovered there was an increase of type 1 narcolepsy (or narcolepsy with cataplexy) cases in a large number of children.

Research linked this outbreak of narcolepsy cases to the Pandemrix flu vaccine. Finnish researchers observed that all of the children who had developed narcolepsy following vaccination also had the narcolepsy risk allele DQB1*0602/DRB1*15. This research was supported by other studies conducted in the region. This research suggests that the Pandemrix vaccine interacted with genetic susceptibility factors to trigger childhood narcolepsy.

Autoimmune Diseases and Cross-Reactivity

Recent research provides new insights into the relationship between the Pandemrix vaccine and narcolepsy. A new study suggests that cells in the blood of narcolepsy-susceptible individuals mounted a strong immune response to two of the peptides found within the vaccine. These two peptides are known as H1N1 virus neuraminidase and nucleoprotein. Following vaccination, when immune cells (T cells) were primed by H1N1 virus peptides, these peptides cross-reacted with proteins found within the central nervous system.

Generally speaking, cross-reactivity is when the proteins in one thing are similar to the proteins in another thing. Swine flu virus neuraminidase is similar to a protein found within the human body: protein-O-mannosyltransferase 1 (POMT1). When the Pandemrix vaccine was given to people, it likely caused the body to attack its own POMT1 protein. The increase in type 1 narcolepsy cases in children after vaccination suggests that POMT1 is an autoantigen in type 1 narcolepsy. An autoantigen is a normal protein or other substance in the body that causes the body to launch an immune response. In this case, the body might have mistaken POMT1 for a foreign substance and tried to fight it. This is how an autoimmune disease essentially works: The body does not recognize the protein as its own and attacks it.

Altogether, this chain of events likely led the genetically susceptible children’s bodies to mount an immune response after vaccination. This immune response ultimately attacked the hypocretin-producing cells in the hypothalamus of the brain, which caused cataplexy and other symptoms of narcolepsy.

Is H1N1 a Risk Factor for Narcolepsy?

If the Pandemrix vaccine was able to trigger narcolepsy in some people, can the H1N1 virus do the same? Research in mice supports this idea. In one study, mice that genetically lacked certain immune cells and were then exposed to H1N1 developed symptoms similar to those seen in people with narcolepsy. While this isn’t the same as human narcolepsy, it does support the idea that H1N1 may initiate an autoimmune response.

Another compelling study was conducted in China following the 2009 swine flu pandemic. Researchers observed that the number of cases of narcolepsy onset was 3-fold greater than usual following the peak of the H1N1 pandemic. Further, children in China were not vaccinated with the Pandemrix vaccine, suggesting that H1N1 itself may be a seasonal risk factor for narcolepsy. However, more research is needed to confirm this seasonality effect.

New Approaches in Narcolepsy

The Pandemrix vaccine's contributing role in the development of narcolepsy in children was unfortunate. If there is any silver lining, it's that scientists did learn more about the nature of the disease: specifically, more about the autoimmune nature of narcolepsy and the potential role that POMT1 may play.

This knowledge may lead to new insights into diagnosing narcolepsy and further advancing treatments for the condition. For instance, it may be useful to measure POMT1 levels in the blood of children with a family history of (or genetic risk factors for) narcolepsy. Targeting POMT1 may also prove to be a useful therapeutic option. However, more research is needed to clarify the role of POMT1 in type 1 narcolepsy.

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Allen J. Blaivas, D.O. is certified by the American Board of Internal Medicine in Critical Care Medicine, Pulmonary Disease, and Sleep Medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Brooke Dulka, Ph.D. is a freelance science writer and editor. She received her doctoral training in biological psychology at the University of Tennessee. Learn more about her here.

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