Een nieuwe studie van Klimas en anderen bevestigt immunologische afwijkingen in ME/CVS:

inflammatie/immuunactivatie (significante toename van de Th1-cytokines IFN-γ and TNF-α), een poging van het afweersysteem om die inflammatie te dempen/tot stilstand te brengen,

getuige de toename van IL-10, FoxP3 en T-suppressor cellen (CD4+CD25+ T cellen),

een verminderde werking van NK-/cytotoxische T-cellen, wellicht mede het gevolg van een afgenomen produktie van granzyme A en K, en een verlaagd aantal CD56bright NK-cellen.

Opvallend detail uit deze studie is de toegenomen genexpressie voor perforine,

omdat in een eerdere studie van Klimas en kollega's bleek dat

de intracellulaire koncentratie van perforine in NK-/cytotoxische afgenomen is.

Een mogelijke verklaring zou kunnen zijn dat er na afloop van het produktieproces

(genexpressie: het omzetten van genetische kode naar eiwitten) iets mis gaat,

net als bij RNase-L dat door proteolyse (via elastase etc.) "verknipt" wordt.

Enkele relevante citaten uit deze studie:

Th1 cells secrete cytokines IFN-γ and IL-2

while Th2 cells secrete cytokines IL-4 and IL-10 [32] and

Th17 secrete pro-inflammatory IL-17a, IL-17f and IL-22 [33, 34].

Recent data on cytokine networks in CFS/ME show

a predominant Th2/anti-inflammatory profile in CFS/ME

with a weakened Th1 profile [17].

This study supports the presence of

a possible imbalance in Th1/Th2 response in CFS/ME characterised by

a significant increase in IL-10 together with significant increases in IFN-γ and TNF-α.

Such increases in IL-10 are suggestive of a persistent chronic infectious state

and may be associated with a dampening of the NK and CD8+T cell immune response.

Nonetheless, increased levels of IL-10, IFN-γ and TNF-α

indicate the presence of fungal, bacterial or viral infection.

Incidentally in HIV elevation in IL10, IFN-γ and TNF-α

denote the presence of a chronic infection and this correlated with viral load.

The increased expression of IL-10 and the relatively higher expression of FoxP3

together with significant increases in CD4+CD25+Tregs suppressive activity

suggest a requirement to counter a significant proinflammatory response in these patients.

Conclusions

These results illustrate

a severely compromised immunomodulation mechanism in CFS/ME

where attempts to regulate or restore immune homeostasis appear to be impaired.

Immunological abnormalities as potential biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis.

Credits/Source: Journal of Translational Medicine 2011, 9:81. doi:10.1186/1479-5876-9-81.

Ekua W Brenu, Mieke L van Driel, Don R Staines, Kevin J Ashton, Sandra B Ramos, James Keane, Nancy G Klimas and Sonya M Marshall-Gradisnik.

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)

is characterized by severe prolonged fatigue, and

decreases in cognition and other physiological functions,

resulting in severe loss of quality of life,

difficult clinical management and high costs to the health care system.

To date there is no proven pathomechanism

to satisfactorily explain this disorder.

Studies have identified abnormalities in immune function

but these data are inconsistent.

We investigated the profile of markers of immune function (including novel markers)

in CFS/ME patients.

Methods:

We included 95 CFS/ME patients and 50 healthy controls.

All participants were assessed on

natural killer (NK) and CD8+T cell cytotoxic activities,

Th1 and Th2 cytokine profile of CD4+T cells,

expression of

vasoactive intestinal peptide receptor 2 (VPACR2),

levels of NK phenotypes (CD56bright and CD56dim) and

regulatory T cells expressing FoxP3 transcription factor.

Results:

Compared to healthy individuals,

CFS/ME patients displayed

significant increases in IL-10, IFN-gamma, TNF-alpha, CD4+CD25+ T cells,

FoxP3 and VPACR2 expression.

Cytotoxic activity of NK and CD8+T cells and

NK phenotypes, in particular the CD56bright NK cells

were significantly decreased

in CFS/ME patients.

Additionally

granzyme A and granzyme K expression were reduced

while

expression levels of perforin were significantly increased

in the CFS/ME population relative to the control population.

These data suggest

significant dysregulation of the immune system

in CFS/ME patients.

Conclusions:

Our study found immunological abnormalities

which may serve as biomarkers in CFS/ME patients

with potential for an application as a diagnostic tool.

http://www.translational-medicine.com/content/pdf/1479-5876-9-81.pdf