Narcolepsy: welcome to neuroimmunology!

A recent report in Science Traslational Medicine (1) has deserved a lot of attention by mainstream media. Headlines referred to it as the confirmation that narcolepsy is an autoimmune disease. Narcolepsy is an interesting disease both clinically (sleep attacks, cataplexy, sleep paralysis, visual hallucinations during early sleep and awakening…) and pathophysiologically. Current knowledge points at a selective death or damage in the neurons of the anterior part of the hypothalamus responsible of orexin production. Orexin (or hypocretin) is a secreted proteic neurotransmitter that regulates awakeness and apettite and whose levels in CSF are significantly lower in patients with narcolepsy than in controls. As usual, the exact cause of narcolepsy is unknown, although recent studies suggest that an autoimmune response, probably triggered by an environmental factor (let’s say, a virus), is the key process in its development (2).The paper by De la Herrán-Arita and colleagues reports an interesting, well-performed study that, contrary to what mainstream media say, does not demonstrate that narcolepsy is an autoimmune disease. But we’ll come to that later. The autoimmune hypothesis of narcolepsy is not new at all. Among the genes that have been associated to narcolepsy, most play important roles in the immune system (3). The strongest association was found with the HLA-DQB1*0602 allele, which more than 95% of the narcolepsy patients carry. But other genes, related to the immune system have also been implicated (4). However, as in any other complex disease, genes don’t explain everything. What the HLA system does is to present antigens (the targets of an immune response, regardless of it is against a pathogen or an autoimmune one) to T cells (lymphocytes) and T cells are the ones enabled to kill a cell carrying that antigen or to call other cells so they are the ones killing the antigenic cell.  One

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