Kerr en kollega's hebben een nieuwe genexpressie-studie gepubliceerd,
waaruit blijkt dat:
- de expressie van 88 genen inderdaad afwijkt (bevestiging),
- de genexpressie van depressieve mensen
niet veel afwijkt van gezonde mensen, en
dus sterk afwijkt van die van patiënten met ME/CVS,
- ME/CVS-patiënten op basis van genexpressie
in 8! subgroepen onderverdeeld kunnen worden
met duidelijke verschillen in klinisch beeld (symptomen) en
- er subtype-specifieke verschillen zijn m.b.t. EBV- en enterovirus-infekties:
twee vaak voorkomende triggers voor ME/CVS.
Citaten uit het uitgebreide studierappport:
Various groups have analysed
the gene expression in
peripheral blood of
patients with CFS/ME and
in all of these studies,
genes of immunity and defense are prominent.
Of the 88 genes,
84 were found to be upregulated and
4 were downregulated (HIF1A, IL7R, PAPOLA, SHPRH),
which is similar to what we reported previously.
The fact that only
5 of these genes were abnormally expressed in endogenous depression patients
as compared with normals,
supports the view
that CFS/ME and endogenous depression are biologically distinct, and
that the psychological features of CFS/ME are in fact secondary to the pathogenesis.
The clinical phenotype was distinct between subtypes;
Subtype D
was the most severe,
having the lowest scores for
SF36 modules RP, VIT, GH, BP and Total score, and
the highest frequency of occurrence of muscle pain and sleep problems.
Subtype B was the least severe,
having the highest scores for
SF36 modules RP, GH, MH and total score.
Subtype B had
a higher median score for
the SF36-RP (physical role)
than all the others combined.
[SF36 RP: fysiek funktioneren, GH: gezondheid algemeen, MH: geestelijke gezondheid]
However,
subtype B
had the highest frequency of
cognitive dysfunction, muscle weakness and post-exertional malaise.
Subtype B
showed
a higher frequency of cognitive dysfunction
than all non-subtype B patients combined and
showed
an increased severity and duration of headache
compared with all non-subtype B patients combined.
Subtype B also had
a higher median score for mental fatigue (Chalder scale)
than all non-subtype B patients combined
although this did not reach significance.
Subtypes B and C
had the best mental health scores, and
subtypes A and F had the worst.
Subtype E
had a higher median score for SF36-VIT (vitality)
than all the others combined
Subtype E
had the highest frequency of GI problems.
Patients of subtype F
showed
a higher frequency of
increased severity of numbness/tingling
compared with all non-subtype F patients combined.
Patients of subtype H
showed
an increased frequency of
severity of sore throat
compared with all non-subtype H patients combined.
In the normal persons,
the predominant category of
EBV serostatus was late phase of infection,
while in the CFS/ME subtypes,
the predominant category of
EBV serostatus was primary/reactivation,
which was seen in subtypes A, B, C, D, F and H.
With all 12 genes,
there was a trend which did not reach significance.
However, when GABPA and EGR1were removed from the analysis,
the remaining 10 genes showed a striking association with subtype.
It is particularly interesting that
5 of 6 CFS/ME patients with Q-CFS/ME clustered in the same subtype (subtype A).
Microbial infections in eight genomic subtypes of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME).
J Clin Pathol. 2009 Dec 2. [Epub ahead of print]. doi:10.1136/jcp.2009.072561.
Zhang L, Goudh J, Christmas D, Mattey D, Richards S, Main J, Enlander D, Honeybourne D, Ayres J, Nutt DJ, Kerr J.
We have previously reported
genomic subtypes of
CFS/ME
based on
expression of
88 human genes.
In this study
we attempted to
reproduce these findings,
determine
specificity of
this signature to CFS/ME, and
test for associations
between CFS/ME subtype and
infection.
We determined
expression levels of
88 human genes
in blood of
61 new patients
with idiopathic CFS/ME
(according to Fukuda criteria),
6 patients with Q-fever associated CFS/ME from the Birmingham Q-fever outbreak
(according to Fukuda criteria),
14 patients with endogenous depression
(according to DSM-IV criteria) and
18 normal blood donors.
In patients with CFS/ME
differential expression
was confirmed
for all 88 genes.
Q-CFS/ME patients
had similar patterns ofgene expression
to idiopathic CFS/ME.
Gene expression in
endogenous depression patients
was similar to that in the normal controls,
except for upregulation of five genes (APP, CREBBP, GNAS, PDCD2, PDCD6).
Clustering of
combined gene data
in CFS/ME patients
for this and
our previous study
(n=117 CFS/ME patients)
revealed genomic subtypes
with distinct differences in
SF-36 scores,
clinical phenotypes,
severity and
geographical distribution.
Antibody testing for
Epstein-Barr virus (EBV), enterovirus, Coxiella burnetii and parvovirus B19
revealed
subtype-specific relationships for EBV and enterovirus,
the two most common infectious triggers of CFS/ME.
PMID: 19955554 [PubMed - as supplied by publisher]
Uitgebreid studieverslag:
http://jcp.bmj.com/cgi/rapidpdf/jcp.2009.072561v1.pdf
Met dank aan Rob
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