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Afwijkende genexpressie

in speeksel

duidt op hoofdrol

inflammatie, immuunactivatie,

immuundysfunctie

en oxidatieve stress.†

 

 

 

 


 

 

 

 

Een onderzoek van Lucacchini en collega's naar de verschillen in genxepressie tussen een patiŽnt

en zijn gezonde tweelingbroer impliceert dat inflammatie, immuunactivatie, immuundysfunctie,

een verminderde stofwisseling en verhoogde oxidatieve stress voorname afwijkingen in ME/CVS zijn.

 

Overigens bleek de patiŽnt op vrijwel alle cognitieve testen lager te scoren dan zijn tweelingbroer.

 

Weliswaar betrof het onderzoek slechts ťťn patiŽnt en ťťn gezonde proefpersoon,

maar de auteurs stellen daar tegenover dat alle afwijkingen aan de ziekte gerelateerd lijken te zijn.

 

 

 

 


 

Citaten uit de studie m.b.t. de rol van de gevonden afwijkingen:

 

 

[V]iral infections have been discovered to promote the secretion of CYPA

supporting the hypothesis that

a persistent viral infection may contribute to the pathogenesis of CFS.

 

...

 

[I]g alpha-1 chain C has a role in preventing access of

foreign antigens to the general immunologic system.

 

PIgR ensures humoral defense in the mucosa against incoming pathogens

and it is responsible for intracellular neutralization of some viruses

through its secretory component.

 

...

 

Psoriasin [S100A7] has been associated with

increased inflammatory cell infiltrates

in breast cancer and various inflammatory disorders

 

...

 

Our results showed an

up-regulation of cystatin B, and a down-regulation of cystatin C.

 

These two cystatins belong to

two different subtypes of cystatin, type I and II respectively.

 

It was demonstrated that they have different functions, e.g.,

type I cystatins are up-regulated in tumor tissue

while type II cystatins are generally down-regulated in tumors.

 

Therefore, we believe our findings could suggest that

the balance between cysteine proteinases and their inhibitors is impaired in CFS.

 

...

 

14-3-3 proteins are involved in a wide range of pathological processes

and by means, the increase is probably not CFS-specific.

 

...

 

[W]e observed a down-regulation in CFS of ZAG.

 

...

 

[A] role of ZAG in the activation of AMP kinase (AMPK),

an important regulator of energy metabolism,

in human skeletal muscle cells has emerged.

 

[T]he decrease of ZAG that we found in WS seems to support

the hypothetical role of oxidative stress in CFS.

 

From the same point of view we can explain

the increase of 6-phosphogluconate dehydrogenase in WS of CFS.

 

This is an enzyme of the oxidoreductase class that allows the production of NADPH

which is necessary for protection against reactive oxygen species.

 

 

 


 

 

A multidisciplinary approach to study a couple of monozygotic twins

discordant for the chronic fatigue syndrome: a focus on potential salivary biomarkers.

J Transl Med. 2013 Oct 2;11(1):243. doi: 10.1186/1479-5876-11-243.

Ciregia F, Giusti L, Da Valle Y, Donadio E, Consensi A, Giacomelli C, Sernissi F, Scarpellini P, Maggi F, Lucacchini A, Bazzichi L.

 

 

Abstract

 

 

BACKGROUND:

 

Chronic Fatigue Syndrome (CFS) is a severe, systemic illness

characterized by persistent, debilitating and medically unexplained fatigue.

 

The etiology and pathophysiology of CFS remains obscure,

and diagnosis is formulated through the patient's history and exclusion of other medical causes.

 

Thereby, the availability of biomarkers for CFS could be useful for clinical research.

 

In the present study, we used a proteomic approach to evaluate

the global changes in the salivary profile

in a couple of monozygotic twins who were discordant for CFS.

 

The aim was to evaluate differences of salivary protein expression

in the CFS patient in respect to his healthy twin.

 

 

METHODS:

 

Saliva samples were submitted to

two-dimensional electrophoresis (2DE).

 

The gels were stained with Sypro, and

a comparison between CFS subject and the healthy one was performed

by the software Progenesis Same Spot including the Analysis of variance (ANOVA test).

 

The proteins spot found with a >= 2-fold spot quantity change and p < 0.05

were identified by nano-liquid chromatography electrospray ionization tandem mass spectrometry.

 

To validate the expression changes found with 2DE of 5 proteins

(14-3-3 protein zeta/delta, cyclophilin A, Cystatin-C, Protein S100-A7, and zinc-alpha-2-glycoprotein),

we used the western blot analysis.

 

Moreover, proteins differentially expressed were functionally analyzed

using the Ingenuity Pathways Analysis software

with the aim to determine the predominant canonical pathways and the interaction network involved.

 

 

RESULTS:

 

The analysis of the protein profiles allowed us to find

13 proteins with a different expression in CFS in respect to control.

 

Nine spots were up-regulated in CFS and 4 down-regulated.

 

These proteins belong to different functional classes,

such as inflammatory response, immune system and metabolism.

 

In particular, as shown by the pathway analysis, the network built with our proteins

highlights the involvement of inflammatory response in CFS pathogenesis.

 

 

CONCLUSIONS:

 

This study shows the presence of differentially expressed proteins in the saliva of

the couple of monozygotic twins discordant for CFS, probably related to the disease.

 

Consequently, we believe the proteomic approach could be useful

both to define a panel of potential diagnostic biomarkers and

to shed new light on the comprehension of the pathogenetic pathways of CFS.

 

 

http://www.translational-medicine.com/content/pdf/1479-5876-11-243.pdf