Chronic fatigue is not all in the mind
21 July 2005
NewScientist.com news service
AT LONG last, we are beginning to get to grips with chronic fatigue syndrome. Differences in gene expression have been found in the immune cells of people with the disease, a discovery that could lead to a blood test for the disorder and perhaps even to drugs for treating it.
The symptoms of chronic fatigue syndrome have been compared to those of a really bad hangover: extreme weakness, inability to think straight, disrupted sleep and headache. But unlike a hangover, the symptoms linger for years, devastating people’s lives.
While nobody doubts CFS exists, just about every aspect of it is controversial. Some say it is the same as myalgic encephalomyelitis, or ME; others disagree. Many specialists are convinced it does have a biological basis, but pinning down physical abnormalities common to all patients has proved tough. People with CFS have often received little sympathy from doctors who dismiss it as “all in the mind”.
“The study shows some aspects of chronic fatigue syndrome may be understood in molecular terms. It is not a ‘made-up’ illness”Now Jonathan Kerr’s team, which is moving to St George’s University of London, has compared levels of gene expression in the white blood cells of 25 healthy individuals with those in 25 patients diagnosed as having CFS according to strict criteria. The researchers found differences in 35 of the 9522 genes they analysed using DNA chip technology.
The few similar studies done in the past have produced conflicting results, so the team double-checked their results using a more accurate method called real-time PCR. That confirmed that 15 of the genes were up to four times as active in people with CFS, while one gene was less active. The results will appear in the Journal of Clinical Pathology next month.
Kerr is repeating the study in 1000 CFS patients and healthy controls, this time looking at 47,000 gene products. So far, the larger study backs up the earlier results, he told New Scientist.
If Kerr really has succeeded where many have failed, and identified clear physical changes in people with CFS, the lingering opinion that it is “all in the mind” could finally be laid to rest. “This exciting new work shows that some aspects of this complex illness may be understandable in molecular terms, and that CFS is not a ‘made up’ illness,” says Russell Lane, a neurologist at Charing Cross Hospital in London.
It should also be possible to develop a blood test for CFS. The team has already discovered differences in blood proteins related to the changes in gene expression.
Kerr hopes the work might even lead to treatments. “We have shown that a significant part of the pathogenesis resides in the white blood cells and in their activity,” he says. “It will open the door to development of pharmacological interventions.”
Several of the genes identified by the team in CFS play important roles in mitochondria, the power factories of our cells. “The involvement of such genes does seem to fit with the fact that these patients lack energy and suffer from fatigue,” Kerr says.
One of these gene products, EIF4G1, is involved in protein production in mitochondria. It is hijacked by some viruses, so cells may compensate by ramping up gene expression. “I am excited by the paper,” says Basant Puri, a CFS expert at Hammersmith Hospital in London. “The group’s finding of upregulation of EIF4G1 is consistent with subclinical persistent viral infection.”
This fits in with the idea that CFS is sometimes triggered by viruses such as Epstein-Barr, Q fever, enteroviruses and parvovirus B19. “CFS often begins with a flu-like illness which never goes away,” Kerr says.
Of the other genes whose expression varies in CFS patients, some are involved in regulating the activity of the immune system. Others play important roles in nerve cells, including a gene called NTE, which codes for an enzyme affected by organophosphates and nerve gases.
Journal reference: Journal of Clinical Pathology (vol 58, p 823, 860)
From issue 2509 of New Scientist magazine, 21 July 2005, page 9
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