For most healthy people, falling asleep or just sacking in during a business meeting or a gathering with friends or while driving a car is a horror scenario. For patients with narcolepsy/cataplexy this is every day’s reality. They suffer from an overwhelming daytime sleepiness, uncontrollable sleep attacks and cataplexy or a sudden loss of muscle tonus after any intensive emotion such as for example laughter. There is no cure for this disease available, only various stimulants and drugs suppressing the sleep can help to ease and improve the symptoms.
The body attacks itself
Sleep researcher Emmanuel Mignot and his team at the Center for Narcolepsy at Stanford University in Palo Alto, California, now found out that two genes of the immune system are responsible for narcolepsy which leads to the assumption of an autoimmune genesis. The results of their study were published in the professional magazine Nature Genetics.
For 20 years already, the scientists are conducting casual research. In the late nineties they discovered that patients with narcolepsy lack hypocretin. Only few brain cells in the hypothalamus produce the neurotransmitter which keeps man and beast awake. Although the hormone production of patients suffering from the disease functions they still lack the producing cells. The loss of cells already gave rise to the suspicion of a destroying process. In addition narcoleptics showed a specific variation of the human leukocyte antigen (HLA). HLA stimulates the immune response by presenting fragments of pathogens to immune cells to fight them eventually. Many autoimmune diseases are HLA associated.
Researchers find more gene variants
In their latest research, Mignot and the geneticist Joachim Hallmayer at Stanford University analyzed DNA of nearly 4,000 participants. All showed the HLA associated with narcolepsy but only half of them actually suffered from it.
Narcolepsy patients are distinguished from healthy people by consistent gene variants in the area of the T-cell receptor alpha (TCRA)-gene which encodes a receptor protein on the surface of T-cells, the mobile combat group of the immune system. The gene is responsible for communicating to the T-cells of the immune system how to react to pathogens presented by the HLA. HLA-TCR-interactions contribute to organ specific autoimmune processes and co-regulate a large part of the immune response.
It remains unclear why T-cells lay specific hypocretin cells, just like the triggers of the self-destroying attacks remain untold – like in almost all autoimmune diseases.
Group with increased risk
In a press release of the US-National Institute of Neurological Disorders and Stroke (NIH) about the study, the publishers emphasize: It is important to note that this study, like most genome-wide association studies, did not identify genetic variants that directly cause narcolepsy-cataplexy. In people with the HLA variants that predispose to narcolepsy-cataplexy, there is about a 20-fold higher frequency of the disorder if variants in the TCRA-gene are present, like for example some Asian populations and African Americans.
The findings could also lead to a discovery of other risk factors. Further characterizations of T-cells could help reveal whether specific environmental factors – such as infections – contribute to the disorder. The researchers hope now for a better understanding of other autoimmune diseases where HLA genes are known to play a role.