Is Narcolepsy an Autoimmune Disorder?

Narcolepsy is a neurological disorder that affects your sleep-wake cycle. We still don’t know what is causing the disease. But most people with type 1 narcolepsy – the kind with sudden muscle weakness or cataplexy – have little or no orexin. Also called hypocretin, it is a chemical in the brain that controls arousal.

Now there is growing evidence that an autoimmune process could trigger this loss.

Birgitte Kornum, PhD, Associate Professor in the Department of Neuroscience at the University of Copenhagen, studies sleep and the immune system. She did not find any specific antibody linked to narcolepsy, but “the autoimmune hypothesis is the best explanation which captures all of the findings we have so far.”

Most research is done on type 1 because it is much more common and there is a loss of hypocretin.

“There has been a lot of time and money spent identifying an autoimmune antibody,” says Vahid Mohsenin, MD, sleep medicine specialist at Yale Medicine and professor of medicine at Yale School of Medicine in Connecticut. . “But nothing has been proven to be specific enough to explain any type of narcolepsy, whether it’s type 1, type 2, or something in between.”

Here is what we know.

The autoimmune hypothesis

Your immune system protects you against germs, including viruses and bacteria. But sometimes he thinks that your own cells could hurt you or make you sick. Thus, it attacks them as well as other healthy tissue. This is called autoimmunity.

Certain types of immune cells called T cells are involved in this process. CD4 + and CD8 + T cells are building blocks of autoimmunity, explains Insoo Kang, MD, a rheumatologist at Yale Medicine in Connecticut. These cells can cause damage on their own or by helping other immune cells.

Studies, including Kornum’s research, have shown that people with narcolepsy have CD4 + and CD8 + T cells that are autoreactive to hypocretin neurons. This means that these T cells can detect and target the cells that make hypocretin.

This does not prove that these T cells are the ones that destroy hypocretin. “But it all goes in the same direction: there is something in the immune system that specifically targets these neurons, and they are lost,” says Kornum.

Other autoimmune diseases, such as type 1 diabetes, also have self-reactive CD8 + T cells. Kornum says researchers are comparing the two conditions because of their similarities.

Other factors at play

People with type 1 narcolepsy are much more likely to have mutations or changes in a group of genes called human leukocyte antigen (HLA). But you can still have narcolepsy with a normal HLA gene. And some people without narcolepsy have a mutated HLA gene. This makes the genetic part of narcolepsy “interesting and confusing,” Mohsenin says.

As with other health issues, it’s likely that your genes and your environment influence each other. Mohsenin points to the events of the 2009 H1N1 flu epidemic. He says some countries used a flu vaccine that we did not use in the United States. These regions experienced a peak in cases of narcolepsy compared to previous years.

Some experts believe that a protein in this flu vaccine, or the infection itself, reacted with the hypocretin-producing cells. And studies show that people who have the HLA gene for narcolepsy have a higher antibody response to this protein. “This is another piece of circumstantial evidence indicating immunity in narcolepsy,” Mohsenin says.

Kornum agrees that narcolepsy is probably a mix of “unfortunate” factors. She says it includes your genes, your T cells, and external triggers, like a viral infection like the flu.

“The thought right now is that in order to develop the disease, you need a combination of everything. This is why you can see elements in healthy people, but they did not have everything at the same time.

Where is the research going?

There is more to learn about the most important genetic changes to increase your chances of narcolepsy. And Kornum says there is “a lot of effort to better understand the picture of T cells.” One way to do it, she says, could be better animal and mouse models that mimic the human autoimmune process.

Researchers also tried to determine whether drugs targeting the immune system – immunomodulators – could treat narcolepsy. But Mohsenin says those experiments have yet to work. Part of the problem is that once you lose hypocretin, it goes away. Or at least it seems that way. And no drug can replace it.

Future treatment and diagnosis

The autoimmune link does not change the way doctors currently manage narcolepsy. But it could happen on the road.

“There is both hope that we can treat (narcolepsy) by targeting the immune process, and there is also hope that all of this research could come from better biomarkers,” Kornum said.

A biomarker is something specific to a disease that can be measured. If the experts find one for narcolepsy, “you could be diagnosed with a blood sample instead of all those expensive and time-consuming procedures we have today,” says Kornum.

But today, doctors still treat narcolepsy by reducing the symptoms. That’s because “we really have no idea what the mechanism of narcolepsy is – what causes it and what really is the crux of the problem,” Mohsenin says.

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