An international team of researchers has found evidence that the GlaxoSmithKline Pandemrix flu vaccination – which was widely distributed during the 2009 swine flu pandemic – may have caused rare cases of narcolepsy. Their study, which was published July 1 in Science Translational Medicine, described that the vaccination stimulated antibodies to attack receptors in brain cells that help regulate sleep.
Lawrence Steinman, a professor of pediatrics and of neurology and neurological sciences at the Stanford University School of Medicine, and his collaborators sought to determine why the Pandemrix vaccine
The researchers found that H1N1 contains a protein highly similar in structure to a portion of a human hypocretin receptor. Thus antibodies that are normally generated to target the flu protein, the researchers theorized, could also incidentally target hypocretin receptors, which are involved in regulating sleep-wake cycles in the brain, and cause an autoimmune reaction.
Steinman said, “It was a really exciting moment for all of us that the difference could potentially be explained by an autoimmune reaction.”
In order to test their hypothesis that the narcoleptic patients had such antibodies, the team worked with Finnish health authorities and examined a sample of 20 individuals who developed narcolepsy after the Pandemrix vaccination. Seventeen of them had elevated antibodies to the hypocretin receptor, while among the six individuals immunized with Focetria none had these antibodies. The researchers attribute this to the fact that compared to Pandemrix, Focetria contains 72 percent less of the H1N1 protein, and therefore does not appear to have stimulated specific flu antibodies capable of binding to the receptor.
According to the study, Pandemrix, which was given to more than 30 million Europeans, strongly suggested to trigger an autoimmune reaction that led to narcolepsy in some people who are genetically at risk. The researchers propose a “hit-and-run” mechanism where high levels of the H1N1 protein stimulate the production of large amounts of antibodies, which may remain in the blood for months, to both the virus and the hypocretin receptor. Under certain conditions, the blood-brain barrier can be altered, allowing the antibodies to enter the brain where they latch onto hypocretin receptors, possibly targeting these brain cells destruction by the immune system.
These results have provided new insights into the nature of narcolepsy, but Steinman stated that the team’s results have still not elucidated the exact cause or completely proven it is an autoimmune disorder. Based on these results, they can simply theorize that narcolepsy may be caused by a similar mechanism that occurred in this case, since narcoleptic patients have very low levels of the neurotransmitter hypocretin and neurons that produce hypocretin.
Steinman described this finding as a “first step” in their pursuit to nail down the cause of narcolepsy. In the future, the research team plans to induce narcolepsy in animal models and compare different vaccines.
According to Steinman, these findings have provided the first piece of evidence that narcolepsy could potentially behave in autoimmune fashion and may be triggered by a combination of genetic predisposition and infection. He, along with his collaborators, hopes to continue to investigate the cause of narcolepsy.
Contact Rishab Ramapriyan at rishabram ‘at’ gmail.com.