Narcolepsy is a sleep disorder that chronically impacts between 135,000 and 200,000 people in the United States and is thought to go undiagnosed often. It’s characterized by disrupted nighttime sleep, excessive daytime sleepiness, sleep paralysis, hallucinations, and a few other symptoms. Narcolepsy has been thought of us an autoimmune disorder and is strongly linked to genetic alleles that encode for immune proteins. New research has now shown that people suffering from narcolepsy carry autoreactive cells, supporting the hypothesis that this sleep disorder is due to a problem with autoimmunity.
This work, by scientists at the Faculty of Health and Medical Sciences at the University of Copenhagen and the Technical University of Denmark and Rigshospitalet has been reported in Nature Communications.
Our immune system can recognize foreign invaders in our body and destroy them. Serious problems start when it incorrectly decides that our normal cells are foreign and should be attacked. In narcolepsy, neurons that produce the hormone hypocretin and regulate wakefulness are probably targeted for attack.
“We have found autoreactive cytotoxic CD8 T cells in the blood of narcolepsy patients. 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,” explained Associate Professor Birgitte Rahbek Kornum from the Department of Neuroscience.
“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,” Kornum added.
The researchers assessed blood samples donated by twenty volunteers with narcolepsy, and and 52 healthy individuals. In almost every narcolepsy patient, there were autoreactive CD8 T cells. Some of the healthy volunteers also carried those autoreactive cells. In the healthy group, the cells were different, however.
“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,” said Birgitte Kornum.
It may be that some combination of influences like genetics or something in the environment, such as a viral infection, may be the trigger. Now that we know a little more about the cause of the illness, researchers may be able to find better therapeutics.
“Now there will probably be more focus on trying to treat narcolepsy with drugs allaying 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,” noted Kornum.