Sick with Sleep

Narcolepsy may be caused by an autoimmune reaction to hypocretin, the hormone that regulates wakefulness (pictured above) (Image source:

A new study published in Science Translational Medicine suggests that narcolepsy may be connected to a malfunctioning immune system, reports The Scientist. According to the study’s findings, the disorder may arise from the immune system targeting hypocretin, the hormone that controls wakefulness. The results also suggest that a recent GlaxoSmithKline (GSK) flu vaccine may be capable of triggering this autoimmunity, which would explain the emerging connection between receiving the vaccine and developing narcolepsy.

According to The Scientist, a 2009 study (which was partially funded by GSK) initially found a connection between narcolepsy and the immune system by demonstrating that almost all narcolepsy patients share a specific Human Leukocyte Antigen (HLA). HLA molecules are part of the apparatus that presents antigens to T cells, which is how T cells differentiate between the body’s cells and foreign cells, thus deciding which cells are threats and which are safe. The study used sets of twins where only one sibling suffered from narcolepsy to examine how these T cells interacted with hypocretin. Researchers found that T cells from an affected twin would react to hypocretin when presented as an antigen by HLA molecules, but T cells from an unaffected twin would not.

To try and understand the connection between the flu vaccine and narcolepsy, the researchers conducted two experiments. The first examined 10 Irish children who had developed narcolepsy after receiving the GSK vaccine and compared their immune response to hypocretin with their non-narcoleptic siblings who shared the same HLA molecules. Much like with the twins, only the narcoleptic children reacted to HLA-presented hypocretin. This more or less served to demonstrate that in those patients who developed narcolepsy after receiving the flu vaccine, the disorder’s mechanism revolved around T cells reacting to hypocretin. The question now became why.

Hemagglutinin, shown in blue above, may sensitize the body’s immune system to epitopes found on hypocretin, leading to narcolepsy (Image source:

The second experiment looked to answer that question by comparing the structure of the H1N1 virus’ hemagglutinin protein to the structure of hypocretin. If the two were similar, it would explain why receiving the flu vaccine would create an immune response to hypocretin. The group found similar epitopes in each, meaning that developing a sensitivity to H1N1 could create a similar sensitivity to hypocretin, thus leading to narcolepsy.

Beyond drawing a convincing connection between the flu vaccine and narcolepsy, this study establishes a fundamental basis for the sleep disorder. As Steven Black, of Cincinnati’s own Children’s Hospital, told The Scientist, this is the first study to offer a mechanic by which narcolepsy operates. Looking at the disorder as an autoimmune disease could give a new perspective on how to treat and live with narcolepsy. And that’s pretty exciting.

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