New Scientist article on changed gene expression in CFS

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Chronic fatigue is not all in the mind

23 July 2005

NewScientist.com news service

Rowan Hooper

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 peoplewith the disease, a discovery that could lead

to a blood test for the disorderand perhaps even to drugs for

treating it.The symptoms of chronic fatigue syndrome have been

compared to those of areally bad hangover: extreme weakness,

inability to think straight, disruptedsleep 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.

Peoplewith CFS have often received little sympathy from doctors who

dismiss it as " all in the mind " .Now Kerr's team, which is

moving to St 's University of London,has compared levels of

gene expression in the white blood cells of 25 healthyindividuals

with those in 25 patients diagnosed as having CFS according tostrict

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 calledreal-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 inthe 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 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 geneexpression.Kerr hopes the work might even lead

to treatments. " We have shown that asignificant part of the

pathogenesis resides in the white blood cells and intheir activity, "

he says. " It will open the door to development ofpharmacological

interventions. " Several of the genes identified by the team in CFS

play important roles inmitochondria, the power factories of our

cells. " The involvement of such genesdoes seem to fit with the fact

that these patients lack energy and suffer fromfatigue, " Kerr says.

One of these gene products, EIF4G1, is involved in protein production

inmitochondria. 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 ofupregulation

of EIF4G1 is consistent with subclinical persistent viral

infection. " This fits in with the idea that CFS is sometimes triggered

by viruses such asEpstein-Barr, Q fever, enteroviruses and parvovirus

B19. " CFS often begins witha 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)