Narcolepsy involves ‘sleep attacks’ that can interfere with daily activities.
Narcolepsy is a chronic neurological condition that affects a person’s sleep-wake cycle.
The condition makes people feel excessively tired during the day. It may also cause them to experience sudden “sleep attacks,” during which an overwhelming desire to sleep can interfere with daily activities.
According to the National Institute of Neurological Disorders and Stroke, between 135,000 and 200,000 people in the United States are currently living with narcolepsy.
Some of these people also experience cataplexy — that is, “a sudden loss of muscle tone” that usually occurs in response to strong emotions such as laughter or surprise.
Researchers have divided narcolepsy into two subcategories: type 1, which is more common and also involves cataplexy, and type 2, wherein people do not have cataplexy.
In narcolepsy type 1, the neurons that produce a sleep-inducing chemical called hypocretin are damaged. Hypocretin is a neurotransmitter that helps keep the brain alert and stops it from entering the dreaming phase of sleep at the wrong time.
Previous studies have found that a class of immune cells called CD4 T are autoreactive in narcolepsy. This means that they see the body’s own hypocretin-producing neurons as if they were “foreign” bacteria or viruses and attack them.
Now, new research adds to the evidence that narcolepsy is an autoimmune condition. A team of scientists based in Denmark has discovered that CD8 T cells are also autoreactive in narcolepsy.
Birgitte Rahbek Kornum, an associate professor in the Department of Neuroscience at the University of Copenhagen, is the last and corresponding author of the study.
Studying immune cells in narcolepsy
Rahbek Kornum and colleagues analyzed blood samples from 20 study participants who had narcolepsy and 52 participants who did not have narcolepsy (the controls).
The scientists found autoreactive CD8 T cells in almost all of the people with narcolepsy. Interestingly, however, they also found the cells in a lot of the controls.
“We have found autoreactive cytotoxic CD8 T cells in the blood of narcolepsy patients,” reports Rahbek Kornum. “That is, the cells recognize the neurons that produce hypocretin, which regulates a person’s waking state.”
“It does not prove that they are the ones that killed the neurons, but it is an important step forward. Now we know what the cells are after,” says Rahbek Kornum.
“We also found autoreactive cells in some of the healthy individuals, but here the cells probably have not been activated. It is something we see more and more often with autoimmunity — that it lies dormant in all of us, but is not activated in everyone. The next big puzzle is learning what activates them,” adds the researcher.
Toward more effective, precise treatments
Rahbek Kornum goes on to explain that discovering autoreactive immune cells in the control group supports the theory that certain factors are necessary to trigger autoreactivity in narcolepsy. Such factors could be a viral infection, for example.
Such a theory may inform the search for better treatments, she explains. “Now there will probably be more focus on trying to treat narcolepsy with drugs [that target] the immune system.”
“This has already been attempted, though, because the hypothesis that it is an autoimmune disease has existed for many years. But now that we know that it is T cell-driven, we can begin to target and make immune treatments even more effective and precise,” she says.
“To kill other cells, e.g., neurons producing hypocretin, CD4 and CD8 T cells usually have to work together. In 2018, scientists discovered autoreactive CD4 T cells in narcolepsy patients.”
“This was really the first proof that narcolepsy is, in fact, an autoimmune disease. Now we have provided more, important proof: that CD8 T cells are autoreactive too.”
Birgitte Rahbek Kornum