Kerr:

8 subgroepen op basis van afwijkende genexpressie,

met duidelijke relaties met 2 infekties.

 

 

 

 


 

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 patiŽnten met ME/CVS,

  • ME/CVS-patiŽnten 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