Narcolepsy is a disabling sleep disorder that is caused by a lack of cells in the brain that produce hypocretin, a hormone that helps regulate the sleep-wake cycle. People with the disorder suffer from sudden and frequent bouts of daytime sleepiness. It was found in the 1980’s that unique variants of the gene HLA-DQB1*0602 were strongly related to narcolepsy. This gene codes for a protein that presents foreign proteins to the immune system, which becomes activated to destroy pathogens carrying those proteins.However, not everyone with HLA-DQB1*0602 variants has narcolepsy, so Emmanuel Mignot, a sleep researcher at Stanford University in Palo Alto, California, organised a team of scientists together that scanned the entire genome of more than 4,000 people who have the variant gene, to find other genes associated with narcolepsy. Mignot’s team found that the people who did have narcolepsy were 20 times more likely to also have a variant TCR-alpha gene. The TCR-alpha gene codes for a receptor that identifies foreign proteins in the body and triggers the immune system to attack. TCR-alpha receptors found on the T-cells of the immune system, work closely with HLA proteins to recognise and destroy cells that have been identified as foreign. This strongly suggests that the two variant proteins working together can turn the immune system against hypocretin-producing cells, causing narcolepsy. The discovery means that it might be possible to prevent narcolepsy by blocking the variant proteins, so they can't trigger the destruction of hypocretin-producing cells.
Gethin Thomas, an immunologist at the University of Queensland in Brisbane, Australia, said the research was important because, while HLA proteins were known to be involved in dozens of autoimmune diseases, it was the first time anyone had found both a HLA protein and a T-cell receptor linked to an autoimmune disease.
