Saturday, October 18, 2008

Living with CFS/Fibromyalgia

I've gone out two days this week for errands, and have spent a lot of the rest of the week in bed, exhausted.  It's not what I want to do, but I know that if I don't rest, I'll get worse and have to spend a lot more time in bed, trying to get back to baseline.
A friend with fibromyalgia (who is still employable) observed that she will be out Saturday and Sunday, and will spend Monday in bed. 
The problem is not, as with depression, that we have no interest in doing anything, but that we know what will happen if we do go out to do something.  She knows that two full days out-and-about in a row is going to send her to bed.  The nature of her employment allows her to schedule around that knowledge.  The nature of my former employment did not -- I had to work 5 days in a row, I couldn't schedule on-call days with recovery days in between.  Unfortunately, when I attempted to go back to work part-time a few years ago, three days in a row was too much, and I landed back in bed for two days, but as a new employee, I didn't have the clout to demand a schedule of working no more than 2 days in a row without a recovery day; I was already getting all the accommodation they were willing to offer by working part-time instead of full-time.
Everything I do must be weighed against the aftermath.  Is doing this worth a day or two in bed?  There was a flower show a couple weeks ago, it would've been fun, but I didn't want to go badly enough to pay the price of a day or two of feeling worse after being out for a couple of hours. 
The problem with CFS/fibromyalgia is not that you can't go out occasionally, the problem is that the condition is "invisible" because the people who see you when you're out and about don't see what you're like after you get home.  Most mild-to-moderate patients can go out; they're not bedridden.  While I was in remission from 1988-1999, none of my co-workers had any suspicion that there was anything wrong with me.  I could pass for normal during the work day because they didn't see me when I got home and immediately collapsed on the couch.  They had no idea I spent most of the weekend resting.
And even now, I can often pass for normal because I know what my limits are.  Like Cinderella, I have to get home before I turn into a pumpkin.  As long as I stay within my limits, none of the people I pass on the street would have any clue that I'm not healthy.  But if something causes me to stay out beyond "the witching hour", it's as obvious as turning into a pumpkin: I look exhausted, I start to limp, it takes me forever to walk that last few blocks to home.  But if I time it perfectly, I get up the front stairs still moving normally and don't limp till I'm behind closed doors where no one can see
It's really no different from most other medical conditions.  You probably won't know that lady has severe asthma as long as she's sitting down not doing anything strenuous.  You can't tell that man is completely deaf till you try to talk to him.  I know mentally-challenged people who are assumed to be of normal intelligence till they open their mouths.  Even a missing limb is not necessarily immediately apparent with quality prosthetics.  But at some point, it does become obvious that the person is not as healthy as you initially assumed, and the same is true of CFS/fibromyalgia.  Get close enough to a patient that she trusts you with the truth, and it'll be painfully obvious that this is not a well woman, no matter how healthy she looked when you were only seeing her once a month at a one-hour club meeting.
One of my fellow club members doesn't try to tell me I'm imagining things, doesn't treat me like a hypochondriac, doesn't argue "but you look so good"; she knows other fibromites and knows how bad it can be.  No muss, no fuss, she simply makes it seem natural when she gets up to fetch something for me.  It makes perfect sense to anyone watching that if I'm in the corner behind the table, it's logistically easier for her to get up from her seat in front of the table (we just don't admit that I always sit in that back corner for a reason), and she doesn't put up a big showy argument about "you're sick, let me do that for you", just gets up and does it as unobtrusively as possible.  And the way she handles it makes me more likely to accept her help than to bellow "I am not a #$%^$!! invalid, I can get it myself" as I did once with someone who was trying to make sure the whole crowd knew what a saint she was to be looking after me so well. 

Friday, October 17, 2008

Study on CFS and Depression

Factors associated with depression among individuals with chronic
fatigue syndrome: findings from a nationally representative survey.

Journal: Fam Pract. 2008 Oct 3. [Epub ahead of print]

Authors: Fuller-Thomson E [a,b], Nimigon J. [b]

[a] Department of Family and Community Medicine
[b] Factor-Inwentash Faculty of Social Work, University of Toronto,
246 Bloor Street West, Toronto, Ontario M5S 1A1, Canada

Correspondence to Esme Fuller-Thomson, Faculty of Social Work,
University of Toronto, 246 Bloor Street West, Toronto, Ontario M5S
1A1, Canada; Email:

Received 8 December 2007; Revised 29 July 2008; Accepted 29 August 2008.

NLM Citation: PMID: 18836094

OBJECTIVES: Most previous research regarding chronic fatigue syndrome
(CFS) and depression has relied on clinical samples. The current
research determined the prevalence and correlates of depression among
individuals with CFS in a community sample.

METHODS: The nationally representative Canadian Community Health
Survey, conducted in 2000/2001, included an unweighted sample size of
1045 individuals who reported a diagnosis of CFS and had complete
data on depression. Respondents with CFS who were depressed (n = 369)
were compared to those who were not depressed (n = 676). Chi-square
analyses, t-tests and a logistic regression were conducted.

RESULTS: Thirty-six per cent of individuals with CFS were depressed.
Among individuals with CFS, depression was associated with lower
levels of mastery and self-esteem. In the logistic regression
analyses, the odds of depression among individuals with CFS were
higher for females, younger respondents, those with lower incomes and
food insecurity and those whose activities were limited by pain. Two
in five depressed individuals had not consulted with any mental
health professional in the preceding year. Twenty-two per cent of
depressed respondents had seriously considered suicide in the past
year. Individuals with CFS who were depressed were particularly heavy
users of family physicians, with an average of 11.1 visits annually
(95% confidence interval = 10.7, 11.6).

CONCLUSION: It is important for clinicians to assess depression and
suicidal ideation among their patients with CFS, particularly among
females, those reporting moderate to severe pain, low incomes and
inadequate social support.

* * *
If 36% of CFS patients in the study are depressed, then 64% are not depressed.  This shoots down the theory that CFS=depression.
As far as why they're depressed, look at the analysis: "those with lower incomes and food insecurity and those whose activities were limited by pain" were those more likely to be depressed.  DUH!  Poor, starving and physically unable to do the things you want, are not exactly keys to being happy with your life.
I'm one of the majority who are not depressed.  No psych evaluator has ever found any evidence of a psychiatric problem -- they keep sending me back to the doctors with the observation that the symptoms I describe are compatible with a physical illness, and the doctors keep refusing to accept the expert opinion that puts the onus back on them to find out what's really wrong.  It's easier for them to prescribe unneeded anti-depressants and blame the patient when I report that anti-depressants don't help because I'm not depressed.
Other studies have found that the percentage of CFS patients who suffer depression is roughly equal to the percentage in patients who have equally-debilitating/painful illnesses.  CFS patients may be a little more prone to depression than those with other diseases simply because they're constantly bullied and badgered by people who don't believe they're really ill, while other diseases come with public sympathy and support.  A key element of abusive relationships is for the abuser to denigrate the victim until she believes his statements that she's bad/lazy/useless/stupid and loses all self-esteem, and the same is true of CFS patients -- those whose self-esteem is not as solid as mine are very easy to push over the edge into losing self-esteem and qualifying for a depression diagnosis, not because they are "depressed" but because they have been told so often that they're not really sick until they question their own reality and accept the abuser's version. 


Student Research Competition Award

Deadlines extended

Due to increased interest, the abstract submission deadline  for the IACFS/ME Student  Research Award has been extended to Nov. 1. Poster deadline is Jan 15. The award will not be determined prior to the conference as it will be based on the oral/poster presentation. For further information, check the website or you can contact:

Staci R. Stevens, MA
Founding Executive Director
Pacific Fatigue Laboratory
University of the Pacific
Sport Sciences Department
3601 Pacific Avenue
Stockton, Ca  95211
209.946.7649 Tel
209.946.3225 Fax

Please spread the word as this is a good way to stimulate and encourage student research interest.

Jill McLaughlin
IACFS/ME Membership Committee


Report/Video from Conference on Viruses in CFS


Finally, HHV-6 has an ICD-9 code! Three years ago
the HHV-6 Foundation proposed to the CDC
Committee that they establish new ICD-9 codes for
HHV-6 & 7 infections as well as one specific for
HHV-6 encephalitis. Not only did they agree on
HHV-6 & 7, they added HHV-8 as well. Please make
a note of the following ICD-9 codes:

HHV-6 infection: 058.81
HHV-6 encephalitis: 058.21

Conference Report

The 6th International Conference on HHV-6 & 7 and
satellite conference on Viruses in CFS held in
Baltimore June 19- 23rd were very successful, with
over 230 scientists and clinicians in attendance.

Anthony Komaroff, MD of Harvard University kindly
prepared a lay summary (suitable for patients) of
each conference that can be downloaded at the links
below. Scientific summaries will be published soon.

*  Summary of the 6th International Conference on
     HHV-6 & 7, June 20-23rd, 2008 (~jvr: see below)

*  Summary of the Viruses in CFS conference, June
     23-24th, 2008  (~jvr: see the next issues of Help
     ME Circle)

For additional highlights on the conference, click
here: (~jvr: see one of the next issues of Help ME

Conference abstract books & videos.

To purchase an abstract book or a DVD of the
conference, click here:

New papers on HHV-6:

CIHHV-6 in congenital infection. Caroline Hall and
associates at University of Rochester found that 86%
of congenital infections were caused by CIHHV-6 or
chromosomally integrated HHV-6. They also report
that 8% of the CIHHV-6 infants had mRNA,
suggesting that these infants either have a reduced
immune response to HHV-6, or that CIHHV-6 may
activate in some individuals. Click here: to see the abstract from the September issue of

HHV-6A linked to syncytial giant-cell hepatitis. At
the onset of the disease in a transplant patent,
HHV-6A (but not HHV-6B) DNA was found in plasma,
in affected liver tissue, and in the syncytial giant
cells. Viremia disappeared with the resolution of
symptoms. Click here: to see the abstract from the August issue of New
England Journal of Medicine.

Click here:
to see other recent papers of interest.

By Anthony Komaroff, MD

Summary of the 6th International
Conference on HHV-6 & -7

The 6th International Conference on HHV-6 & 7 was
held in Baltimore, Maryland, on June 19- 22, 2008. A
satellite conference on Viruses in Chronic Fatigue
Syndrome and Post-Viral Fatigue followed the main

Biology of Human Herpesvirus-6 (HHV-6)

In order to best diagnose and treat diseases caused
by a virus, it is essential to learn as much as
possible about the virus-its genes and the proteins
made by those genes, as well as how it infects cells
and reproduces itself.

It is known that the first step by which HHV-6 infects
a cell is attachment to a receptor on the surface of
the cell called CD46. New research found that the
CD46 receptor is located on what is called a "lipid
raft", and that the raft carries the virus inside the
cell where it then can make new copies of itself.

It has been unclear where, inside a cell, new viruses
are assembled. One group reported that this occurs
inside little "bubbles" called multivesicular bodies
(MVBs). The MVBs float toward the surface of the cell
and then exit the cell to go on and infect other cells.

Proteins that are unique to HHV-6 were reported
(particularly one called U94), and two proteins
(called IE 1 and IE2) were shown to distinguish the
variants (A and B) of HHV-6.

When cells are infected by HHV-6, the virus
multiplies much more rapidly if the cell is also
infected with another "cousin" herpesvirus, human
cytomegalovirus, or if the infected cell is placed next
to a cell called a dendritic cell.

Chromosomally Integrated HHV-6 (CIHHV-6)

Most herpesviruses remain as little circles of DNA
inside infected cells, separate from the DNA of the
cell's chromosomes. Several years ago it was
reported that HHV-6 could sometimes integrate itself
into a cell's chromosomes, including the
chromosomes of sperms and eggs making it possible
for HHV-6 to be inherited from a parent. At first,
scientists were very skeptical of this, but subsequent
studies convinced most scientists that it was true:
some people had chromosomally integrated HHV-6

How common is CIHHV-6? Evidence presented at the
conference confirmed earlier reports that CIHHV-6 is
present in about 1% of people.

Does CIHHV-6 cause any medical problems? One
reason to think that it could is that in the 99% of
humans without CIHHV-6, only a very small number
of cells are infected with HHV-6. In CIHHV-6, since
the viral DNA was inherited from the sperm or egg of
a parent, the viral DNA is present in every cell.

Nevertheless, many scientists have been skeptical
that CIHHV-6 causes any medical problems. First of
all, there has not been strong evidence that the
complete virus is integrated into the chromosomes,
or that it can produce proteins or make copies of
itself-things viruses typically must do in order to
cause medical mischief.

Several preliminary reports at the conference
indicated that CIHHV-6 may indeed lead to the
production of multiple copies of the virus, and may
cause disease. One research team repeatedly
measured the "viral load"-the amount of viral DNA
in the blood-from a group of patients with CIHHV-6.
If the virus was not capable of reproducing multiple
copies of itself, then it would be expected that the
viral load would remain constant over time. Instead,
the research team found extremely large differences
from one sampling to another, indicating that
sometimes the virus was making many copies of
itself, and sometimes it was not.

Even more compelling were two small studies. One
study involved three patients with CIHHV-6 and
chronic fatigue syndrome. The research team found
that when the three patients were given the antiviral
drug valganciclovir, which kills HHV-6 in laboratory
("test tube") studies, the viral load in their blood
went way down, and their symptoms improved.
Another study involved one patient with CIHHV-6
who suffered from acute encephalitis (inflammation
of the brain, usually caused by an infection), a
neurological condition called myoclonus, and loss of
consciousness. The patient was given another
antiviral drug that kills HHV-6, foscarnet, and
completely recovered.
Still, it will take randomized
trials of these antiviral drugs (or others effective
against HHV-6) in patients with CIHHV-6, evidence
of active HHV-6 infection, and illness that could
plausibly be caused by HHV-6 to prove that CIHHV-6
can cause illness.

Diagnostic Tests

Some progress was reported in diagnostic tests that
distinguish active infection from inactive (latent)
infection with HHV-6, tests to distinguish the A
strain of the virus from the B strain, and tests to
quantify the amount of virus present in a sample.
Still, the field has not reached the point where all
experts can agree on what the best tests are in
specific clinical circumstances.

HHV-6 in Brain Diseases

Soon after HHV-6 was discovered, it became clear
that the virus could cause infection of brain
cells-glial cells and neurons. That raised the
possibility that HHV-6 might play a role in some
brain diseases.


For several years it has been clear that HHV-6 could
produce encephalitis in patients with compromised
immune systems (such as people placed on immune
system suppressing drugs during organ
transplantation, or patients with AIDS). It also has
been clear that the virus can cause temporary
encephalitis in young children when they are first
infected with the virus.

The conference reported increasing evidence that the
virus also can cause encephalitis in adults with
normal immune systems. A study of adults with
encephalitis of unknown cause-people who tested
negative for all known causes of encephalitis-found
that HHV-6 DNA could be identified in the spinal fluid
of 40% of them. In one patient in whom a brain
biopsy was performed, the virus was also found in
the brain.

Multiple sclerosis.

In multiple sclerosis (MS), the "insulation" wrapped
around a nerve cell, called myelin, is damaged by an
autoimmune attack (an attack by one's own immune
system on some part of one's body), compromising
the function of the nerve cell. In 1995, a research
report suggested that HHV-6 might be one trigger of
multiple sclerosis (MS). Since that time, the majority
of the published papers on this subject have been
consistent with the first report.

At the Conference, the following additional
supportive evidence was presented: 1) antibodies
(called "oligoclonal bands") specifically against
HHV-6 were found in the spinal fluid of a minority of
patients; 2) HHV-6 was found to cause a disease like
MS in a monkey (a marmoset); 3) HHV-6 was found
to damage cells called oligodendroglial precursor
cells, cells that repair damage to myelin.


For about 10 years doctors have recognized that
when infants are first infected with HHV-6 the virus
can trigger seizures. At the Barcelona Conference in
2006, preliminary evidence was presented that
HHV-6 might be a trigger for temporal lobe epilepsy
in adults. At the Baltimore Conference, impressive
evidence was presented by many different scientists
that HHV-6 is the most common cause of seizures
occurring when a child has a fever ("febrile
seizures"). It also appears to be the most common
cause of uncontrollable seizures in children (a
condition called "status epilepticus"). It is unclear if
these childhood seizures triggered by HHV- 6 make
the child more vulnerable to seizures or other
neurological conditions in adulthood, although a
study of that question is underway.

More evidence was presented that HHV-6 may trigger
some cases of temporal lobe epilepsy. The strongest
evidence involves brain tissue that has been
surgically removed as a treatment for epilepsy. Two
different research groups reported finding large
amounts of the virus in that brain tissue, particularly
in a region of the brain known to be involved in
temporal lobe epilepsy-the CA1 region of the
hippocampus. The infection primarily involved brain
cells called astrocytes.

Mood disorders.
A team from Japan reported that HHV-6 makes a
protein called SITH-1, and that this protein appears
to cause mood disorders. When, using genetic
engineering, a mouse was modified in such a way
that brain cells called glial cells made large amounts
of SITH-1, the mice behaved in a manic (hyperactive)

Antibodies to SITH-1 were found circulating in the
blood of most patients with major depression,
bipolar disorder ("manic-depression"), and chronic
fatigue syndrome-whereas such antibodies were not
found in any adults without these conditions. In two
adults with mood disorders attributed to encephalitis
caused by HHV-6, unusually large amounts of the
messenger RNA that makes SITH-1 were found. This
preliminary study is intriguing, but much more work
is needed to determine whether HHV-6, or the
SITH-1 protein that it makes, are common causes of
mood disorders.

Chronic fatigue syndrome.

The possible role of HHV-6 in chronic fatigue
syndrome (CFS) is discussed in the summary of the
Viruses in Chronic Fatigue Syndrome and Post-Viral
Fatigue Conference.

HHV-6 and HHV-7 Reactivation in Transplant

Many studies have shown that HHV-6 (and probably
HHV-7) are often reactivated in patients whose
immune systems have been suppressed by medicines
(such as in organ transplantation) or by diseases
(such as AIDS). New studies confirmed that: 1) such
reactivated HHV-6 infection can cause encephalitis;
2) disease is reduced by white blood cells called T
cells that are primed to attack HHV-6; 3) increased
levels of the immune system chemical called
interleukin-6 (IL-6) predict transplant patients that
are more likely to develop encephalitis (and might
therefore benefit from antiviral therapy).

HHV-6 in Drug-Induced Hypersensitivity Syndrome

Investigators reported that HHV-6, HHV-7 and other
herpesviruses are often reactivated during an
unusual and severe type of drug allergy, variably
called either DIHS or DRESS. The illness involves
many different organs (often the brain and the liver),
frequently leads to high numbers of white blood cells
called eosinophils, and is sometimes followed by the
development of type 1 diabetes or autoimmune
thyroid disease (thyroiditis). HHV-6 was found in
diseased tissues, including brain and liver,
suggesting that-once reactivated by the allergic
reaction-the virus might have contributed to the

Another report found that several of the medicines
that most often trigger the severe allergic syndrome
also cause reactivation of HHV-6, suggesting that
reactivation of the virus might even be a primary,
rather than a secondary, cause of the illness. HHV-6
and HHV-7 in Cancer

Several herpesviruses-particularly Epstein-Barr
virus-have been found to cause some kinds of
human cancer. The first step in suspecting a possible
role for a virus in causing cancer is to find the virus
inside the cells that are cancerous-but not in most
of the noncancerous cells nearby. Research groups
reported finding HHV-6 in cells of non-Hodgkin's
lymphoma, Hodgkin's lymphoma, brain tumors called
gliomas and in cells from cancer of the cervix. In
several of these reports, there was a greater amount
of virus in the more malignant cells. While these
reports could indicate that HHV-6 is a factor (or
co-factor, along with other cancer-causing viruses) in
causing these cancers, it also could be an "innocent
bystander", attracted to the cancerous tissue but not
really making the tissue turn cancerous.

Heart Diseases

Two possibly-related diseases of heart muscle,
myocarditis and dilated cardiomyopathy, have no
known cause. Several research teams reported that
HHV-6 (and several other viruses) could be found in
the heart muscle of patients with these diseases,
but only rarely in healthy heart muscle. These
patients often also had evidence of reactivated
HHV-6 infection in white blood cells. In one patient
treated with an antiviral drug effective against
HHV-6, the pumping power of the heart muscle
improved, suggesting that the viral infection might
be causally related to the heart muscle disease.

Even more provocative, one group reported that
HHV-6 can infect the inner lining (called the
endothelium) of the arteries of the heart (the
coronary arteries). Furthermore, they found that
HHV-6 infection causes inflammation in the wall of
the artery. A second group compared patients with
myocarditis that was associated with HHV-6 to those
with myocarditis not associated with HHV-6. There
was a greater tendency in the first group for the
coronary arteries to go into spasm.

Together, these results suggest the possibility that
patients with myocarditis caused by HHV-6 may also
have HHV-6 infection of the lining of their coronary
arteries. That, in turn, could mean that HHV-6 may
play a role in causing or worsening coronary artery
disease-the most important cause of premature
death in adults. While at this time a role for HHV-6
in coronary artery disease is just a remote
possibility, there is some evidence that its "cousin"
herpesvirus human cytomegalovirus-may play a role
in coronary artery disease. There also is strong
evidence that a related herpesvirus, Marek's disease
virus, causes coronary artery disease in birds.

Treatments for HHV-6

Several antiviral drugs-some already available to
treat other viruses and some still
experimental-appear to be very effective against
HHV-6 in laboratory testing. Whether these drugs
will work when used in people with illnesses caused
by HHV-6, and whether they will produce side
effects, remains to be seen.


When HHV-6 was discovered 20 years ago, its
remarkable ability to infect a wide variety of cells
suggested the possibility that it might be capable of
triggering a wide variety of diseases. At this
conference, the expanding spectrum of diseases
associated with HHV-6 (and, in some cases, HHV-7)
was remarkable. While none of these disease
associations has been proven, in every instance the
evidence in favor of the association of HHV-6 and the
disease was stronger than it had been in the past,
and no previously-suggested association was
contradicted by newer and better information.

This makes it imperative that a greater effort be
made to improve diagnostic testing and expand
available treatments.

The HHV-6 Foundation has created a new community on in order to seperate the presentations from the Satellite Conf. on Viruses in CFS from the main HHV-6 Conf.
  Before, the direct link took you to a list of videos where videos from the main conference and the satellite(CFS) conference were mixed together, making it hard to tell the difference between the two. Otherwise, you had to link to each presentation seperately.
  The new link is-


CFS and the Central Nervous System

Chronic Fatigue Syndrome and the Central Nervous System

The Journal of International Medical Research 2008; 36: 867 - 874

Chen R, Liang FX, Moriya J, Yamakawa J, Sumino H, Kanda T, Takahashi T.

An increasing amount of neuroimaging evidence
supports the hypothesis that chronic fatigue
syndrome patients have structural or functional
abnormalities within the brain.

Moreover, some neurotrophic factors, neurotrans-
mitters and cytokines have also been evaluated in
order to elucidate the mechanism of abnormal
neuropsychic findings in chronic fatigue syndrome.

In this review, we suggest that the focal point of
chronic fatigue syndrome research should be
transferred to the central nervous system.

Full-text (free):

* * *
In other words, all those people who've told us "it's all in your head" were right, but not in the way they think!


Fatigue study on Classic ME

A new paper on fatigue in ME (new criteria based on Ramsay's description and definition) has just been published online. This is the first of several research papers on classic ME.

An additional file with the normative data for fatigue will be available on the url below in the next days.

Bulletin of the IACFS/ME
Volume 16, Issue 3 • 2008

Fatigue in Myalgic Encephalomyelitis Ellen M Goudsmit, Bart Stouten, Sandra HowesAbstract

Background: The objectives of this study were to measure fatigue in patients with well-defined Myalgic Encephalomyelitis (ME) and to assess if  there are any problems associated with the Chalder Fatigue Scale, which has been widely used to assess fatigue in patients with chronic fatigue syndrome (CFS).Methods: Twenty-six patients were recruited from a local support group. All had been diagnosed by physicians and met research criteria for ME. They completed  the 11-item Chalder Fatigue Scale and were also asked to rate the severity of their illness. The fatigue scores were calculated using both the Likert method (0,1,2,3) and the bimodal method (0,0,1,1,).
Results: The mean Likert score was 26.65 (SD 5.36) and the mean bimodal score was 9.81 (SD 2.04).  Fifty per cent of the patients recorded the maximum score using the bimodal method and 77% recorded the two highest scores. Moreover, there was a marked overlap between those who rated themselves as moderately or severely ill. These findings are indications of a low ceiling.
Conclusions: The findings from this study using the Chalder Fatigue Scale show that the low ceiling associated with the bimodal method means that this scoring system is not suitable for use in clinical trials.  Researchers may wish to consider alternative instruments to obtain a more accurate measure of fatigue in patients with moderate to severe ME and similar conditions.

Ellen M. Goudsmit PhD CPsychol AFBPsS


Pacing article now online

The review of pacing by Goudsmit and Howes is now available online (open access):

The article begins on p. 46.

Please note that the Belgian report on CFS confuses pacing with APT, which is very different. The latter is consistent with the version of pacing devised for patients with psychiatric problems limiting activity (see textbooks on CBT).

Pacing was tested in the RCT by Wallman et al. It reduces fatigue but has a limited effect, hence should not be offered on its own but as part of a programme. Pacing is an alternative to GET, where activity is planned according to a pre-determined schedule and patients are encouraged to tolerate some discomfort.  Pacing for CFS/ME requires the patients to listen to their body and activity is therefore determined by symptoms. The difference is not what one does but when one stops.
Ellen M. Goudsmit PhD CPsychol AFBPsS


Buy Christmas Cards, Support Research

Buying your Christmas cards from Action for M.E. is a great way to support
our cause.

Action for M.E.'s 2008 Christmas card selection is now available for you to

Those who get our quarterly magazine InterAction will receive a copy of the
brand new Christmas card brochure. If you are not subscribed to our magazine
you can download a copy of the brochure here .

This year we have more designs than ever to choose from and the brochure
contains all the details you will need to place your order.

For information on our personalised Christmas card range click here. 

Last year we raised just under £13,000 through the sale of Christmas cards,
helping to support our campaigning work and information services.

Thank you for your support."

Action for M.E.



6 "Facts" about CFS (and my response)

In the rare event of a problem with registration, or if you have any special
requirements, please contact me at  with
"Registration" in the subject line and I'll make sure that you are connected
as soon as possible. I also welcome any constructive criticisms, or advice
and suggestions, to make things better and better for all of us.


A little feature on the "Your Health" page of That's Life, issue 43, 23
October 2008
(date appears ahead of today because it is a weekly magazine) lists "6 facts
about Chronic Fatigue".

I am writing a response which suggests that, far from being "facts", these
are myths or stereotypes which are spread - perhaps quite unintentionally -
by articles like this.

This does not appear online, so we have typed it on to our website here
which you can read when logged in.

May I suggest that as many as can manage write a response to show that there
are other opinions than the ones printed here.
the email address for the letters page is
the email address for the your health page is

Or you could just laugh your head off at our joke of the day here

Dr John H Greensmith
ME Free For All. org

Your 6 Facts About Chronic Fatigue Syndrome are somewhat un-factual.  See CFS Myths at
CFS and depression share a few symptoms, but CFS shares far more symptoms with the neurological disease Multiple Sclerosis, and some research indicates that CFS and MS may be caused by the same virus.  Researchers have found abnormalities of the central nervous system, autonomic nervous system, and immune system, which are not present in depression, and on certain tests, the results for CFS and depression are diametrically opposite, definitively proving they are not the same thing. 
Anti-depressants and counseling can be helpful for patients who have become depressed by having a debilitating illness, but they do not cure the CFS, any more than they would be expected to cure MS. 
As to the "fact" that "most doctors recommend" exercise, repeated research has found a post-viral heart defect in many CFS patients, which the experts say makes aerobic exercise inadvisable, and a 2005 study found that increasing exercise levels resulted in dramatic increases in symptoms.  A 2008 Belgian study found that treating CFS with exercise and counseling actually resulted in more patients being unable to work!  To the contrary, exercise improves the symptoms of depression and gives depressed patients more energy; this is, in fact, the easiest and lowest-cost way for doctors to differentiate between them in order to get the right diagnosis and provide the right treatment.
I hope those of you who have personal experience will take a moment to write a letter to the editor (and send a copy to Dr. John)

Wednesday, October 15, 2008

Spanish Patient's Blog (in English)

Our friend and collaborator from Madrid, Carlos González
("Carlitos"), has a wonderful blog in which he puts all the tests and
treatments that he has done since he got sick with CFS-ME in 2005.
It's in English! Enjoy:

All the best,

Clara Valverde
President, Liga SFC

Monday, October 13, 2008

Evidence of Inflammatory Immune Signaling in Chronic Fatigue Syndrome:

Evidence of Inflammatory Immune Signaling in Chronic Fatigue Syndrome:
A Pilot Study of Gene Expression in Peripheral Blood

Anne L Aspler, Carly Bolshin, Suzanne D Vernon and Gordon Broderick

Behavioral and Brain Functions 2008, 4:44doi:10.1186/1744-9081-4-44

26 September 2008

Abstract (provisional)

Genomic profiling of peripheral blood reveals altered immunity in
chronic fatigue syndrome (CFS) however interpretation remains
challenging without immune demographic context. The object of this work
is to identify modulation of specific immune functional components and
restruct uring of co-expression networks characteristic of CFS using
the quantitative genomics of peripheral blood.

Gene sets were constructed a priori for CD4+ T cells, CD8+ T cells,
CD19+ B cells, CD14+ monocytes and CD16+ neutrophils from published
data. A group of 111 women were classified using empiric case definition
(U.S. Centers for Disease Control and Prevention) and unsupervised
latent cluster analysis (LCA). Microarray profiles of peripheral blood
were analyzed for expression of leukocyte-specific gene sets and
characteristic changes in co-expression identified from topological
evaluation of  linear correlation networks.

Median expression for a set of 6 genes preferentially up-regulated in
CD19+ B cells was significantly lower in CFS (p=0.01) due mainly to
PTPRK and TSPAN3 expression. Although no other gene set was
differentially expressed at p<0.05, patterns of co-expression in each
group differed markedly. Significant co-expression of CD14+ monocyte
with CD16+ neutrophil (p=0.01) and CD19+ B cell sets (p=0.00)
characterized CFS and fatigue phenotype groups. Also in CFS was a
significant negative correlation between CD8+ and both CD19+
up-regulated (p=0.02) and NK gene sets (p= 0.08). These patterns were
absent in controls.< /DIV> < DIV class= ygrp-content>

Dissection of blood microarray profiles points to B cell dysfunction
with coordinated immune activation supporting persistent inflammation
and antibody-mediated NK cell modulation of T cell activity. This has
clinical implications as the CD19+ genes identified could provide
robust and biologically meaningful basis for the early detection and
unambiguous phenotyping of CFS.

The complete article is available as a provisional PDF. The fully
formatted PDF and HTML versions are in production.

Provisional PDF:

Immunological Aspects of CFS

Source: Autoimmunity Reviews
        Uncorrected proof
Date:   September 15, 2008

Immunological aspects of chronic fatigue syndrome
Lorenzo Lorusso(a), Svetlana V. Mikhaylova(b), Enrica Capelli(c), Daniela
Ferrari(d), Gaelle K. Ngonga(d), Giovanni Ricevuti(e,f,*)
a Department of Neurology, Mellino Mellini Hospital, Chiari, Brescia, Italy
b Russian Children's Clinical Hospital, Moscow, Russia
c Department of Genetics and Microbiology, University of Pavia, Pavia, Italy
d Department of Neurology, Spedali Civili, University of Brescia, Brescia,
e Department of Internal Medicine, Section of Gerontology and Geriatrics,
  University of Pavia, Azienda Servizi alla Persona, IDR S.Margherita, Via
  Emilia 12, 27100 Pavia, Italy
f Cellular Patophisiology and Clinical Immunology Laboratory, IRCCS San Matteo
  Hospital Foundation, Pavia, Italy
* Corresponding author.
  Department of Internal Medicine, Section of Gerontology and Geriatrics,
  University of Pavia, Azienda Servizi alla Persona, IDR S. Margherita, Via
  Emilia 12, 27100 Pavia, Italy. E-mail address:
  (G. Ricevuti).


Chronic fatigue syndrome (CFS) is a specific clinical condition that
characterises unexplained disabling fatigue and a combination of non-specific
accompanying symptoms for at least 6 months, in the absence of a medical
diagnosis that would otherwise explain the clinical presentation. Other
common symptoms include headaches, myalgia, arthralgia, and post-exertional
malaise; cognitive difficulties, with impaired memory and concentration;
unrefreshing sleep; and mood changes. Similar disorders have been described
for at least two centuries and have been differently named neurasthenia,
post-viral fatigue, myalgic encephalomyelitis and chronic mononucleosis.

Recent longitudinal studies suggest that some people affected by chronic
fatigue syndrome improve with time but that most remain functionally impaired
for several years. The estimated worldwide prevalence of CFS is 0.4-1% and it
affects over 800,000 people in the United States and approximately 240,000
patients in the UK. No physical examination signs are specific to CFS and no
diagnostic tests identify this syndrome. The pathophysiological mechanism of
CFS is unclear. The main hypotheses include altered central nervous system
functioning resulting from an abnormal immune response against a common
antigen; a neuroendocrine disturbance; cognitive impairment caused by
response to infection or other stimuli in sentient people. The current
concept is that CFS pathogenesis is a multifactorial condition. Various
studies have sought evidence for a disturbance in immunity in people with
CFS. An alteration in cytokine profile, a decreased function of natural
killer (NK) cells, a presence of autoantibodies and a reduced responses of T
cells to mitogens and other specific antigens have been reported. The
observed high level of pro-inflammatory cytokines may explain some of the
manifestations such as fatigue and flu-like symptoms and influence NK
activity. Abnormal activation of the T lymphocyte subsets and a decrease in
antibody-dependent cell-mediated cytotoxicity have been described. An
increased number of CD8+ cytotoxic T lymphocytes and CD38 and HLA-DR
activation markers have been reported, and a decrease in CD11b expression
associated with an increased expression of CD28+ T subsets has been observed.
This review discusses the immunological aspects of CFS and offers an
immunological hypothesis for the disease processes.

Keywords: Chronic fatigue syndrome - CFS - Immunological pathogenesis -
Cytokines - Autoimmunity - NK cells - Lymphocytes - Adhesion molecules -
Neutrophils - Infection

1. Introduction

The term 'chronic fatigue syndrome' was proposed in 1988 by the United States
Centres for Disease Control to describe a specific clinical condition that
characterises unexplained disabling fatigue and a combination of non-specific
accompanying symptoms [1]. Similar disorders have been described for at least
two centuries and have been differently named neurasthenia, post-viral
fatigue, myalgic encephalomyelitis and chronic mononucleosis [2,3]. Chronic
fatigue syndrome is a diagnosis of exclusion. CFS can be diagnosed after
ruling out other medical or psychiatric causes of chronic fatigue [4-6]. No
clinical examination signs, no diagnostic tests are specific, no definitive
treatments exist for CFS. Recent longitudinal studies suggest that some
people affected by chronic fatigue syndrome improve with time but that most
remain functionally impaired for several years

The estimated worldwide prevalence of CFS is 0.4-1% and it affects over
800,000 people in the United States and approximately 240,000 patients in the
UK [4,10]. However, a recent report pointed to the variability of CFS
prevalence based on differing studies [4,9]. Another important question is
whether CFS is a homogeneous or heterogeneous disorder: various researchers
have called for investigation of subgroups by features such as chronicity,
immunological activity and neurobiology [9-12]. This disorder does not seem
to prevail in definite geographic areas and ethnic groups [8,9,11], but
predominantly affects young adults, with a peak age of onset of between 20
and 40 years, and women, with a female to male ratio of 6:1. Mean illness
duration ranges from 3 to 9 years [4,11,12]. The pathophysiological mechanism
of CFS is unclear. The main hypotheses include altered central nervous system
functioning resulting from an abnormal immune response against a common
antigen; a neuroendocrine disturbance; cognitive impairment caused by
response to infection or other stimuli in sentient people
Heterogeneity within patient groups diagnosed as having CFS suggests multiple
contributing factors to the disorder Fig. 1) [4,6,9,11,18,20-25]. Further
epidemiological studies and differing research approaches will contribute to
evaluating the real incidence of the pathology. The results of an Australian
study, for example, showed that people affected by bacterial and viral
infections have a relatively uniform post infective syndrome that persists
over six months in a minority of patients (12%) with CFS features
[3,16,19,26]. Evidence of enteroviruses infection persistence was founded in
CFS patients [13-15,19,27]. These findings are in agreement with a genetic
basis of the response by subjects with CFS syndrome to an infectious agent

2. Clinical features of CFS syndrome

CFS has no confirmatory clinical signs or characteristic laboratory
abnormalities so the 'gold standard' is defined by disabling chronic fatigue
and characteristic non-specific accompanying symptoms [1,2,8,10]. Current
diagnostic criteria describe CFS as a syndrome of physical and mental
fatigue, usually of acute onset, which is markedly exacerbated by physical
activity. Sometimes a gradual onset is described, in which the symptom
complex develops over weeks or months. Other common symptoms include
headaches, myalgia, arthralgia, and post-exertional malaise; cognitive
difficulties, with impaired memory and concentration; unrefreshing sleep; and
mood changes [1,4,6,11,28]. (Box 1).

3. Immunological hypothesis of CFS syndrome

Two and a half decades after the coining of the term CFS, the diagnosis of
this illness is still symptom based and the aetiology remains elusive. A
consensus regarding the aetiology and pathophysiology of CFS has not yet been
developed [1,4,11,19,20]. The current concept is that CFS pathogenesis is a
multifactorial condition. [1,4,6,16,21,28]. A possible involvement of the
immune system is supported by the observation that the onset of CFS is often
preceded by virus infections and a 'flu-like' illness. Various studies have
sought evidence for a disturbance in immunity. An alteration in cytokine
profile, a decreased function of natural killer (NK) cells and a reduced
responses of T cells to mitogens and other specific antigens
[362,9,13,16,17,22,26-34] have been reported.

The observed high level of pro-inflammatory cytokines may explain some of the
manifestations such as fatigue and flu-like symptoms and influence NK
activity [16,19,23,29,30]. NK cells play an important role at the interface
between innate and adaptive immunity. A decreased NK cell function
[4,10,16,22,28,30] and a correlation of NK impairment with EBV reactivation
has been observed in CFS patients
[22]. A number of factors could be
responsible for a decrease in NK cell activity, namely a shift in NK cell
populations leading to an increase of less active cells, a decrease in levels
of cytokines that modulate NK cell activity or the presence of inhibitory
factors [16,28,31-33]. Maher K. J. and colleagues [26] found significantly
reduced perforin in NK cells of CFS subjects. Perforin is released along
with granzymes, from intracellular vesicles of cytolytic effector cells and
facilitates the passage of these molecules through target cell membranes,
followed by activation of the apoptotic pathways of cell death. Its
deficiency may be a significant factor in the pathogenesis of CFS

Abnormal activation of the T lymphocyte subsets and a decrease in antibody-
dependent cell-mediated cytotoxicity have been described [16,28,31,33,35-37].
An increased number of CD8+ cytotoxic T lymphocytes and CD38 and HLA-DR
activation markers have been reported [2,4,16,19,22,26,28,29,32,34,36,37],
and a decrease in CD11b expression associated with an increased expression of
CD28+ T subsets has been observed [16,17,28,38].

Cytokine dysregulation might be an important factor involved in the
pathogenesis of CFS [29]. Tomoda and colleagues showed that production of
TGF-beta1 protein was significantly depressed in patients with CFS and that
serum levels of IL-10, IL-18, IL-4, TNF-alpha, IFN-gamma, and IL-6 were not
significantly different from those of controls [32]. On the contrary some
previous studies showed higher serum levels of TGF-beta1 in CFS patients than
in the controls [4,34]. A further study reported normal serum levels of
TGF-beta1 [25]. These contradictory outcomes may have resulted from
differences in laboratory methodologies [4,9,10,11,22,29,30]. As regards
cytokine gene polymorphisms, an increase of high TNF-alpha producers
(TNF-857T rare allele) and a significant decrease of low IFN-gamma (874 A/A
phenotype) producers have been shown in CFS patients [29]. Other studies have
suggested that CFS exhibits a Th2 profile of CD4-helper T-lymphocyte
responsiveness: IFN-gamma (inhibitory pathway) production by CD4+ cells is
reduced in CFS patients [19,26-30]. Skowera and colleagues [27] showed a
significant increase in the numbers of CD4+ and CD8+ T cells secreting IL-4
both following polyclonal stimulation and in resting cell populations from
CFS patients.

Levels of serum immunoglobulin G (Gig) and the Gig subclass seem to be
reduced in CFS patients [28,36]. In Some Authors showed decreased IgG1 and
IgG3 levels and others observed deficiencies in a number of Gig subclasses
(IgG1, IgG3 and IgG4) or only in IgG3 levels in some patients [28,33]. These
deficiencies may be correlated with anti-viral activity in patients with CFS,
and may contribute to the pathogenesis of disease.

Other findings include higher frequencies of various autoantibodies
[23,24,28,36]. A significant increase in the numbers of B cells with CD20+
CD5+ phenotype which is correlated with autoantibody production and with CD21
markers that is a ligand for retroviruses was found in patients with CFS
[28]. In 2005, Robertson et al. observed increased numbers of activated
cytotoxic T cells (CD8/CD38; CD8/HLADR) and B subsets with CD20+/CD25+
phenotype [33]. In 2006, Maes and coworkers showed that CFS was characterized
by an IgM-related immune response directed against disrupted lipid membrane
components, by-products of lipid peroxodation, S-farnesyl-L-cysteine, and
NO-modified amino-acids, which are not normally detected by the immune system
and, due to oxidative and nitrosative damage, have become immunogenic [36].
These findings suggest that an underlying infection may be present in these
individuals and that the immune system is chronically activated in response.
A diverse range of viruses including herpes virus reactivation is frequently
observed in CFS and a dysfunctional immune response may play a key role
[3,5,13,14,16,18,21,26,28,30,32,34,37]. Therefore the question remains
whether virus reactivation triggers CFS in a subset of patients or viral
infection reactivation is yet another outcome of a CFS episode triggered by
other agents. On the basis of the observation that the immune alteration
pattern of CFS has a striking resemblance to the one caused by developmental
immune toxicology, it has been suggested that this disease could be the
consequence of environmental insults (xenobiotic, infectious agents, stress)
to the developing immune system [3,6,21,30,35,38,39].

A role of vaccinations as co-triggers for the development of functional
disorders including fibromyalgia, in conjunction with other contributing
factor was also proposed [3,6,12,24,30].

New data supporting the involvement of the immune system arise from gene
expression studies [17,29,36,37]. Genes that are active in the immune
response have been found to be differentially expressed in all studies of
gene expression in CFS. Most of these genes are crucial for T-cell
activation: CD2BP2, IL-10RA, moesin and cathepsin C; ITGA and NFATC3, or
associated with other immunologic functions (CMR35 antigen, IL-8, HD protein)
[17,36,37], or involved in mechanisms that fights infection (RNase L) [40].

4. Conclusion

The lack of objective biochemical and/or cellular diagnostic markers has
resulted in considerable confusion in diagnosing the syndrome and in
scientific investigation of its aetiology and pathophysiology. The diagnosis
of CFS is highly problematic since no biological markers specific to this
disease have been identified. CFS is a misunderstood, debilitating condition
of unknown aetiology. Results suggest a common link between the central
nervous system, infection, and the immune system. Present data from various
sources support the model that CFS has a propensity to over-produce
proinflammatory cytokines, coupled with a misregulation of anti-inflammatory
cytokines. CFS patients seem to have a specific immune dysfunction profile
with enhanced baseline activation of lymphoid subsets but suppression of
certain immune responses, particularly Th1-driven ones (anti-viral,
anti-tumour responses).
On the basis of these findings, some therapeutical
approaches have been proposed with a view to controlling immune activation

Some researchers suggest that alteration of the immune response profile may
be the consequence of environmental insults in early life development
[21,38,39]. If this hypothesis is confirmed, monitoring for toxicants
adversely affecting the immune system in early life could help prevent the
disease. The variability observed when measuring immunological parameters
suggests a genetic basis for the pathology and could be considered in
attempting to elucidate the mechanism and in developing novel treatments in
patients with CFS.

New findings arising from gene expression studies have confirmed the
activation of certain genes related to immune function and are candidate
markers of the disease.

Figure Caption

Fig. 1. Pathogenesis CFS.


Box 1. Diagnostic criteria for chronic fatigue syndrome
1. Fatigue
    Clinically evaluated, unexplained, persistent or relapsing fatigue
    persistent for six months or more, that:
    - is of new or definite onset;
    - is not the result of ongoing exertion;
    - is not substantially alleviated by rest;
    - results in substantial reduction in previous levels of occupational,
    - educational, social or personal activities; and
2. Other symptoms
    Four or more of the following symptoms that are concurrent, persistent
    for six months or more and which did not predate the fatigue:
    - Impaired short term memory or concentration -- 90%
    - Headaches of a new type, pattern, or severity -- 90%
    - Sore troat -- 85%
    - Tender cervical or axillary lymph nodes -- 80%
    - Muscle pain and multi-joint pain without arthritis -- 75%
    - Feverishness (75%)
    - Unrefreshing sleep -- 70%
    - Psychiatric problems (65%)
    - Rapid pulse (10%)
    - Post-exertional malaise lasting more than 24 h.

Take-home messages
- Patients with CFS appear to have a variety of abnormalities in their
  immune cells that support the presence of an underlying immunological
- These immunological findings show that patients with CFS may have an
  infection and that the immune system is chronically activated in response.
- Several of the differentially expressed genes are related to immunological
  functions and implicate immune dysfunction in the pathophysiology of
  disease. Once identified, these genes could serve as CFS biomarkers.
- A clear understanding of the mechanism of CFS is needed to develop
  treatments that will cure most cases of the disease.


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IL-17F in CFS

Source: Biochemical and Biophysical Research Communications
        Uncorrected proof
Date:   September 4, 2008

Lower frequency of IL-17F sequence variant (His161Arg) in chronic fatigue syndrome patients
Kristine Metzger(a), Marc Fremont(a,*), Chris Roelant(a), Kenny De Meirleir(b)
a Protea Biopharma, Z.1-Researchpark 100, 1731 Zellik, Belgium
b Vrije Universiteit Brussel, Department of Human Physiology and Medicine,
  Pleinlaan 2, 1051 Brussels, Belgium
* Corresponding author. Fax +32 2 481 5311.
  E-mail address:  (M. Fremont).

Article history: Received 25 August 2008


Chronic fatigue syndrome (CFS) is characterized by immune dysfunctions
including chronic immune activation, inflammation, and alteration of cytokine
profiles. T helper 17 (Th17) cells belong to a recently identified subset of
T helper cells, with crucial regulatory function in inflammatory and
autoimmune processes. Th17 cells are implicated in allergic inflammation,
intestinal diseases, central nervous system inflammation, disorders that may
all contribute to the pathophysiology of CFS. IL-17F is one of the
pro-inflammatory cytokines secreted by Th17 cells.
We investigated the
association between CFS and the frequency of rs763780, a C/T genetic
polymorphism leading to His161Arg substitution in the IL-17F protein. The
His161Arg variant (C allele) antagonizes the pro-inflammatory effects of the
wild-type IL-17F. A significantly lower frequency of the C allele was
observed in the CFS population, suggesting that the His161Arg variant may
confer protection against the disease. These results suggest a role of Th17
cells in the pathogenesis of CFS.

Keywords: Chronic fatigue syndrome - CFS - Th17 cells - IL-17F - Polymorphism
- Intestinal dysfunction

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Chronic fatigue syndrome (CFS)/myalgic encephalomyelitis is defined by a
severe and debilitating fatigue associated with a variety of symptoms
including musculoskeletal pain, sore throat, tender lymph nodes, sleep
abnormalities, neurocognitive problems [1]. The pathogenesis of CFS is still
poorly understood, but is likely to be multifactorial; viral infections,
stress, neuroendocrine dysfunctions, exposure to toxins have all been
proposed as contributing factors to the onset and maintenance of the disease

A large body of evidence supports the implication of chronic immune
activation and other immunological dysfunctions in CFS. Decreased NK cell
activity [3] and dysregulation of interferon pathways [4] have been observed
in CFS patients. Increased oxidative stress levels have been detected, which
is consistent with a chronic inflammatory situation [5]. Decreased NK cell
activity, increased allergic and autoimmune manifestations in CFS suggest a
Th2-oriented cytokine pattern [6], a hypothesis supported by the observations
that IFN-gamma production is decreased, whereas IL-4 production is increased
in CFS patients [7-9]. Genetic predispositions may contribute to alterations
of cytokine profiles in CFS patients: a first study of cytokine gene
polymorphisms found an association between CFS and the frequency of TNF-857
and IFN-gamma 874 rare alleles [10].

Another class of cytokines may be relevant in the context of CFS: those
associated with T helper 17 (Th17) cell function. Th17 cells have recently
been identified as a new subset of T helper cells, in addition to the
traditional Th1 and Th2 subsets. Differentiation of Th17 cells from naïve
CD4+ T cells requires the coordinate action of the pro-inflammatory cytokine
IL-6 (produced by activated macrophages/dendritic cells), and of the
immunosuppressive cytokine TGF-beta. Differentiated Th17 cells produce
IL-17A, IL-17F, IL-22, which appear to mediate host response to specific
infections (extra-cellular bacteria), and to play crucial regulatory
functions in inflammatory and autoimmune processes [11-14]. A common variant
of IL-17F, His161Arg, has been characterized; this variant lacks the ability
to activate cytokine production in target cells, and confers protection
against the pro-inflammatory effects of wild-type IL-17F [15]. The Arg/His
amino acid substitution is determined by a T/C polymorphism in the IL-17F
gene (rs763780).

Th17 cells have been implicated in pathologies that share certain symptoms
with CFS: inflammatory bowel disease, rheumatoid arthritis, allergic
inflammation [16-18]. To investigate the role of Th17 cells, and more
specifically of the cytokine IL-17F, in the pathogenesis of CFS, we studied
the association between CFS and the frequency of the IL-17F His161Arg
variant. The rs763780 polymorphism was analyzed in 89 CFS patients, compared
with 56 healthy controls.

Subjects and methods

Eighty-nine CFS patients (40 p/m 12 year old) were enrolled in the study. All
were diagnosed for CFS according to the clinical criteria kolom5 of Fukuda et
al. [1]. Fifty-six aged-matched controls (37 p/m 12 year old) were also
recruited. Seventy-nine percent of the patients, and 70% of the controls,
were females. All subjects were of European origin.

Genomic DNA was extracted from whole blood using the Blood and Tissue DNA
extraction kit, Qiagen (Venlo, Netherlands). Analysis of the rs763780
polymorphism was performed with the SNPlexTM genotyping technology, Applied
Biosystems (Foster City, CA, USA). Genotyping analyses were performed by
DNAvision S.A. (Charleroi, Belgium), using ISO17025-accredited procedures.

Results and discussion

We found a significantly lower prevalence of the His161Arg variant in the CFS
population, compared to the control population
. Eight out of 89 patients
have a CT genotype (8.9%), versus 14 out of 56 controls (25%). None of the
CFS patients have the CC genotype, versus 2 out of 56 controls (3.6%). In
total, 28.5% of the controls have a CC or CT genotype versus only 8.9% of the
patients (OR=4.05, p=0.0018).

The observed lower frequency suggests an involvement of IL-17F, and more
generally of Th17 cells, in the pathophysiology of CFS
. The His161Arg variant
antagonizes the pro-inflammatory effects of wild-type IL-17F, and thereby
exerts a protective effect against asthma [15]. Similarly, we can make the
hypothesis that the development and/or maintenance of CFS involves an
increased production of IL-17F, and that expression of the inactive variant
confers protection against the disease.

Increased IL-17F production has been observed in various inflammatory
[11,15]. Interestingly, it also occurs in the context of
intestinal disease, such as Crohn's disease or ulcerative colitis [19].
Intestinal dysfunction is a common symptom in CFS. Alterations of the
intestinal microbial flora have been reported [20]; such alterations can lead
to intestinal mucosal dysfunction, increased intestinal permeability (leaky
gut), that will finally cause an immune response to the LPS of gram-negative
enterobacteria [21,22]. Exposure of immune cells to LPS could therefore be
the clue to the chronic immune activation observed in CFS patients.
Considering this hypothesis, it is particularly noteworthy that in addition
to IL-6 and TGB-b, optimal Th17 cell induction requires the action of
Toll-like receptor (TLR)-activated peripheral blood mononuclear cells
(PBMCs). TLR-activated monocytes may contribute to Th17 cell induction by
cell-cell contact, through ligation of the T-cell receptor [23];
alternatively, TLR-activated PBMCs may secrete a specific set of cytokines
that will potentiate Th17 induction [24]. In this last report, it was shown
that TLR-4 (receptor for LPS), as well as TLR-7/8, evoked the most robust
induction of Th17, whereas stimulation of TLR-1, -2, -3 or -9 was not

Th17 cell induction could therefore be the link between exposure to
enterobacterial LPS and the symptoms of chronic inflammation associated with
CFS. Interestingly, Th17 and Th1 responses are mutually exclusive, since
IFN-gamma suppresses IL-17 and vice-versa [11]. Th17 induction is therefore
consistent with a decreased production of Th1 cytokines, as seen in CFS. The
proinflammatory effects of Th17-secreted cytokines are also consistent with
other specific dysfunctions observed in CFS patients: IL-17 and IL-22 can
disrupt the blood-brain barrier; Th17 lymphocytes transmigrate across the
blood-brain barrier endothelial cells and promote inflammation of the central
nervous system [25]. Blood-brain barrier permeability and CNS inflammation is
thought to be a key aspect in the pathogenesis of CFS [26].

The implication of Th17 cell activation in the pathogenesis of CFS would be
a significant progress in the understanding of the disease, opening new
therapeutic perspectives. Confirmation of our results on a larger number of
samples is therefore warranted. Further genetic studies will also look at
other IL-17F-related genes, such as IL-23R. IL-17F is indeed specifically
produced by IL-23R-expressing Th17 cells; IL-23R is also polymorphic and some
variants of this receptor predispose to inflammatory bowel disease [16,19].
An association between CFS and polymorphisms of the IL-23R gene, or other
functionally related genes, would provide additional support for the
implication of intestinal dysfunction and IL-17 axis in the pathogenesis of


This work was supported by Grant IWT-070559 from the Instituut voor de
Aanmoediging van Innovatie door Wetenschap en Technologie in Vlaanderen
(IWT). We thank Dr. Patricia Lienard and Roser Sens Espel, from DNAvision
S.A., for their help in designing the genotyping experiment.


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Enteroviral Myalgic Encephalomyelitis

Thanks to Tom for this one....
Enteroviral myalgic encephalomyelitis - EvME [ME/CFS].

A treatise on EvME by Dr. Irving Spurr who argues that "The enteroviruses, ubiquitous in nature, are responsible for a variety of human diseases ranging from mild gastroenteritis to fulminating multi-organ failure. They are the cause of myalgic encephalomyelitis, and it is no surprise that this disease has multi-organ involvement with protean manifestation."
In "Clinical and scientific articles and films" on ME Research UK website


Dr Spurr spoke at the Invest in ME 2008 conference.
A DVD set of the conference including his talk can be purchased at:

The dvd set can either be the PAL or the NTSC system (NTSC is the video
system or standard used in North America and most of South America)
* * *
This fits in with other research.  Dr. Bruno points out that polio (which is related to ME) is a known enterovirus which produces similar symptoms/after-effects.
Enterovirus means "stomach virus" and my first symptoms were a bad case of stomach flu, therefore, I have no doubt that this is correct, and this is what I had..