Dr. Alan Light en kollega's van de universiteit van Utah hebben aangetoond dat
de genenxepressie van ME(CVS)-patiŽnten na een kleine inspanning
duidelijk afwijkt van die van gezonde mensen.
Die afwijkende genenexpressie is
al 30 minuten na de inspanning waarneembaar en
na 48 uur nog steeds aanwezig.
Die afwijkende expressie betreft met name genen
(klik hier) die betrekking hebben op:
- het signaleren van afvalprodukten (metabolieten) die, zeker in kombinatie,
spierpijn en -vermoeidheid doen veroorzaken: melkzuur etc.:
m.n. de ASIC3 (klik hier), P2X4, P2X5-receptor.
- het afweersysteem! :
m.n. IL-10/Th2-response, TLR4 en CD19-markers op afweercellen, bijv. makrofagen.
- het sympathisch zenuwstelsel
(klik hier en
hier voor een toelichting),
met name het afgeven en afremmen van neurotransmitters, bijv. glutamaat).
Er werd een duidelijke relatie gevonden
tussen de afwijkende genenaktiviteit en de fysieke en mentale vermoeidheid en pijn.
Van belang is nog op te merken dat
inspanning door ME(CVS)-patiŽnten de produktie van interleukine 10 (IL-10)
de vaak al aanwezige Th1►Th2-shift nog verder doet versterken,
ook inflammatie het aantal ASIC3 receptoren doet verhogen (klik hier) en
de studie een klein aantal mensen betrof/op grote schaal herhaald zal moeten worden.
Deze studie toont "de onjuiste geloofsovertuiging" aan van van Houdenhove, Nijs e.a.:
- "een onjuiste geloofsovertuiging t.a.v. pijn":
- "een biopsychosociale verklaring voor wijd verspreide pijn":
Aug 09 CFIDSLink:
Breaking Research News (preview!)
Gisteren om 12:10
Blood Biomarkers for CFS: A Light at the End of the Tunnel
By Suzanne D. Vernon, PhD
Scientific Director of the CFIDS Association of America
is an indicator of
a biologic state used
to objectively measure processes
in the body
that occur during
in response to treatment.
Researchers studying CFS have been looking for blood biomarkers
diagnosis of CFS
would not have to rely on self-reported symptoms
that are difficult
to measure by objective means.
a consistent and reproducible blood biomarker
that could be turned into a clinical test
would be a huge leap forward for care and credibility.
Powerful molecular tools have been developed
that now allow
the activity of thousands of genes
to be examined at one time and
to quantify how much gene activity there is
by measuring the amount of message RNA (mRNA).
More than 10 CFS studies
have measured blood gene activity and
found differences between people with CFS and healthy controls,
showing promise of
an objective blood test for CFS.
However, even though investigators
between CFS subjects and
there was little consistency between the 10 studies,
making it difficult
to use any of the identified gene activity differences as biomarkers.
In what could be a groundbreaking discovery for CFS,
Alan R. Light, PhD,
and his team at the University of Utah Health Sciences Center
that increase in activity
following moderate exercise.
The paper was e-published ahead of print on July 30, 2009,
and will appear in an upcoming issue of the Journal of Pain.
These results as presented in this paper
stand out as ďsmart scienceĒ for several reasons.
the investigatorsí logic
is based on mouse experiments
to understand sensory muscle fatigue and pain.
These animal studies showed that
there are molecular receptors
that act together
to detect the metabolites
produced by muscle contraction.
the investigators used
the findings from mouse experiments
for examining the blood in CFS patients and controls
to look for activity of genes
shown to detect metabolites
that result from using muscles.
they used the kind of moderate, full-body exercise
that is known to cause post-exertion fatigue in CFS
but is well-tolerated by healthy control subjects.
The study included
19 CFS patients (15 women and 4 men) and
16 matched controls (11 women and 5 men).
68 percent of the CFS patients
also met the criteria for fibromyalgia.
Each subject was asked to
exercise on an Airdyne bicycle
(uses both arms and legs to turn the wheel)
for 25 minutes.
Blood was collected
before exercise started and
24 hours and
Heart rate and
perceived level of effort
throughout the exercise challenge.
The mRNA was extracted from the blood samples and
gene activity was analyzed
using the TaqMan Gene Expression Assays
manufactured by Applied Biosystems, Inc.
In the laboratory they analyzed
metabolite-detecting genes (ASIC3, P2X4, P2X5),
adrenergic genes (A2A, B-1, B-2, COMT), and
immune system genes (IL6, IL10, TNF alpha, TLR4 and CD14).
When the investigators
compared the activity of these genes
there was no difference
between CFS patients and
as early as 30 minutes after exercise,
there were significant increases in gene activity for
the ASIC3, P2X4, P2X5 metabolite-detecting genes,
the B-1, B-2 and COMT adrenergic genes, and
the IL10, TLR4 and CD14 immune system genes.
The gene activity increases
persisted for up to 48 hours after exercise
in the CFS patients.
As anticipated with moderate exercise,
no gene activity increase
in the healthy subjects.
The activity of these nine genes
could be used
most of the CFS patients
from the control subjects.
confirm previous studies
that have found differences and
the immune system and
the hypothalamic-pituitary-adrenal (HPA) axis
and suggest that
CFS patients have problems with
this study suggests that
a blood test for muscle fatigue and pain is possible.
For these blood biomarkers to be validated,
the numbers of CFS patients and controls will have to be expanded, and
comparisons will need to be made
against subjects with other fatiguing and painful conditions.
The results reported in this paper were supported by a grant from the NIH.
In late 2008,
the Light team
was awarded a grant
from the CFIDS Association of America
to expand the number of subjects and
validate these blood biomarkers in other CFS patient populations.
You can read the summary of that study,
being led by Dr. Kathleen Light,
The Lightsí clinical collaborator is expert CFS clinician Dr. Lucinda Bateman of Salt Lake City.
"Moderate Exercise Increases Expression for Sensory, Adrenergic, and Immune Genes in Chronic Fatigue Syndrome Patients But Not in Normal Subjects."
Light AR, White AT, Hughen RW, Light KC.
Journal of Pain. 2009 Jul 30. [Epub ahead of print]
Moderate Exercise Increases Expression for Sensory, Adrenergic, and Immune Genes in Chronic Fatigue Syndrome Patients But Not in Normal Subjects.
J Pain. 2009 Oct;10(10):1099-112. doi:10.1016/j.jpain.2009.06.003.
Light AR, White AT, Hughen RW, Light KC.
Chronic fatigue syndrome (CFS)
is characterized by
often accompanied by widespread muscle pain
that meets criteria for fibromyalgia syndrome (FMS).
Symptoms become markedly worse after exercise.
Previous studies implicated
the sympathetic nervous system (SNS), and
immune system (IS)
in CFS and FMS.
We recently demonstrated that
acid sensing ion channel (probably ASIC3),
purinergic type 2X receptors (probably P2X4 and P2X5) and
the transient receptor potential vanilloid type 1 (TRPV1)
are molecular receptors
in mouse sensory neurons
that cause acute muscle pain and
possibly muscle fatigue.
These molecular receptors
are found on human leukocytes
along with SNS and IS genes.
Real-time, quantitative PCR showed that
19 CFS patients
had lower expression of
beta-2 adrenergic receptors
did not differ from
16 control subjects
After a sustained moderate exercise test,
greater increases than
in gene expression
for metabolite detecting receptors
ASIC3, P2X4, and P2X5,
for SNS receptors
alpha-2A, beta-1, beta-2, and COMT and
IS genes for IL10 and TLR4
lasting from 0.5 to 48 hours (P < .05).
were also seen in
the CFS subgroup
with comorbid FMS and
were highly correlated with
symptoms of physical fatigue, mental fatigue, and pain.
These new findings suggest
metabolite detecting receptors
as well as SNS
in CFS and
Muscle fatigue and pain
are major symptoms of CFS.
After moderate exercise,
show enhanced gene expression
for receptors detecting muscle metabolites and
for SNS and
which correlate with
These findings suggest
possible new causes,
points for intervention, and
objective biomarkers for these disorders.
Met dank aan Brigitte die me op de studie opmerkzaam maakte.