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.
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.
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.
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.
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.