Originally posted on the Nature news blog. 

A paper that once promised to help unravel a medical mystery — why some children developed narcolepsy after receiving an influenza vaccine — has been retracted.

Narcolepsy is a disorder that causes extreme sleepiness, sometimes inducing uncontrollable ‘sleep attacks’ that can strike at any time of day. In 2010, a puzzling cluster of sudden-onset narcolepsy cases was reported in Europe among children vaccinated with GlaxoSmithKline’s Pandemrix flu vaccine against the H1N1 ‘swine flu’ that had caused a pandemic in 2009.

On December 18, 2013, researchers reported a possible connection between the vaccine and narcolepsy. In a paper published in Science Translational Medicine, they showed that people with narcolepsy produce immune cells called T cells that recognize hypocretin, a neurotransmitter that regulates wakefulness. People with narcolepsy tend to have low levels of hypocretin in neurons that control wakefulness, and the results supported the notion that autoimmune responses could be destroying the neurotransmitter.

The authors, led by immunologist Elizabeth Mellins and narcolepsy researcher Emmanuel Mignot of the Stanford School of Medicine in Palo Alto, California, went on to demonstrate that pieces of a flu protein often used in vaccines stimulated immune cells that recognize hypocretin. This suggested a mechanism by which the vaccine could contribute to narcolepsy in some people.

But on July 31, the authors announced that they have been unable to repeat a key finding: that immune cells from people with narcolepsy respond to hypocretin more so than immune cells from people who do not have narcolepsy. “Because the validity of the conclusions reported in the study cannot be confirmed, we are retracting the article,” the team wrote.

The retraction is a setback for a field struggling to find an answer. “We continue to believe that the original scientific hypothesis remains a valid one that needs to be further explored,” said GlaxoSmithKline, a London-based pharmaceutical firm, in a statement. The company says that it is supporting research, including in its own labs, to explore the possible link between its vaccine and narcolepsy, and particularly to learn more about interactions between the vaccine and other risk factors in the people who developed the condition.

Those risk factors were a mystery even before the retraction. And although the paper suggested a possible link between flu vaccines and narcolepsy, it did not clarify why Pandemrix, in particular, would be problematic. The original study was also conducted in a relatively small number of people.

Given such small numbers, the retraction comes as little surprise, says immunologist Outi Vaarala of the Finland National Institute for Health and Welfare in Helsinki. Vaarala, who praises the authors for openly addressing the problems with their paper, also notes that the methods use to assay immune responses are difficult to reproduce, and says reviewers should demand that researchers repeat their experiments using multiple methods. “If you can show differences in T-cell reactivity between patients and controls when different read-outs are used,” she says, “the findings are likely to be reliable.”

This article is reproduced with permission and was first published on July 31, 2014.