The cause underlying the 2009 phenomenon that left 1,300 persons with incurable narcolepsy has finally been elucidated.
Ahmed SS, Volkmuth W, Duca J, et al. Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor. Science Translational Medicine. 01 Jul 2015; 7(294):294ra105. DOI: 10.1126/scitranslmed.aab2354.
Vogel G. Why a pandemic flu shot caused narcolepsy. Science. 1 July 2015 DOI: 10.1126/science.aac8792.
The Pandemrix influenza vaccine, used in Europe during the 2009 influenza epidemic, caused more than 1,000 cases of incurable narcolepsy.
Now a study by rheumatologist Syed Sohail Ahmed and colleagues has figured out why.
A peptide on the surface of the influenza virus shares protein residues in common with a fragment of the hypocretin receptor 2.
People with the HLA-DQB1*0602 haplotype developed both protective immunity to influenza and an autoimmunereaction to hypocretin receptor 2. This caused the death of the cells and narcolepsy which is presently untreatable.
Hypocretin is a neurotransmitter which regulates and promotes wakefulness, and defects in the hypocretin gene and receptor are a cause of narcolepsy. Many people who develop narcolepsy, and all of the people who developed narcolepsy from Pandemrix, have HLA-DQB1*0602.
An exposed region of the H1N1 influenza nucleoprotein A has residues in common with a fragment of the first extracellular domain of hypocretin receptor 2.
The blood serum of Finnish patients who developed narcolepsy after vaccination with Pandemrix usually bound to cells that were engineered to display the influenza nucleoprotein A and the human hypocretin receptor 2. Serum from Italians who had been vaccinated with a different vaccine, Focetria, did not bind. Focetria contained less of the nucleoprotein.
An increase in narcolepsy followed the 2009 influenza pandemic in China, but causation wasn’t clearly established there.
There were 1,300 cases out of 30 million doses of Pandemrix. The manufacturer, GlaxoSmithKline, has acknowledged the link, and some patients have been awarded compensation.