Researchers find no link between XMRV and chronic fatigue syndromeBMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e6331 (Published 19 September 2012) Cite this as: BMJ 2012;345:e6331
A study designed to find a definitive answer to the question of whether there is a link between the xenotropic murine leukaemia virus (XMRV) and chronic fatigue syndrome has come up with an unequivocal no. The answer was delivered at an 18 September news conference in New York City, and published in the online journal mBio1.
A 2009 paper by Judy Mikovits published in the journal Science,2 and a subsequent paper by Harvey Alter in Proceedings of the National Academies of the United States of America that identified a similar murine retrovirus, claimed to have established a causal relation with chronic fatigue syndrome.3
Mikovits subsequently was involved in convoluted charges and countercharges of illegal activity and theft by her employer and was briefly jailed.4 Those charges were later dismissed by the court.
Attempts by others to replicate the findings of a link failed to do so, and many came to believe the initial work had been sullied by contamination. But questions remained because the confirmatory studies often used different methods and were underpowered.
The National Institutes of Health, the Centers for Disease Prevention and Control and the Food and Drug Administration commissioned a study under the direction of W Ian Lipkin, a professor of neurology and pathology and director of the Center for Infection and Immunity at the Columbia University Mailman School of Public Health, to definitively answer the question.
Senior investigators from the original studies were involved in the design of the new study. It was “overpowered,” involving 147 patients with the syndrome and 146 matched controls, recruited by researchers at six sites across the country. Analysis was blinded.
Genetic tests that looked for the virus in the blood of the subjects “found no evidence of XMRV or related viruses,” said Lipkin. It is “a very clean result that is impossible to misinterpret.”
“There was a finding of some antibody responses” in both groups of subjects, he said, “but no association between the presence of those antibodies and disease.”
“It took extraordinary courage” for the original investigators to participate in this study Lipkin said. “I cannot think of a single instance where an investigator came back, went through this sort of a process, and then stood up and said ‘I made an error here but am committed to moving forward.’”
An advocate of a link between chronic fatigue syndrome and XMRV expressed disappointment that lymph node biopsies were not part of the study and asked whether the murine virus may have been present in a tissue compartment.
“It is theoretically possible . . . but it would be extremely unusual to have a systemic illness not to spill into the blood or leukocyte preparations,” said Alter. The National Institutes of Health researcher played a leading role in discovering the hepatitis C virus.
“One has to resist the temptation to keep the murine retroviral hypothesis alive,” he said. “This study was really quite definitive.”
Lipkin believes chronic fatigue syndrome “is likely to be a constellation of disorders, not necessarily a single agent, be it viral, bacterial, or otherwise.”
He called the samples gathered during this process “an extraordinary resource for addressing questions related to the causes, the treatment, the management, the pathogenesis, the basic sciences of these disorders.”
The NIH has established a process by which qualified investigators can access the stored samples and it is funding further examination of them.
Cite this as: BMJ 2012;345:e6331