CFS Discordant monozygotic twins show potential saliva markers

[snowathlete]

A multidisciplinary approach to study a couple of monozygotic twins discordant for the chronic fatigue syndrome: a focus on potential salivary biomarkers.

http://www.translational-medicine.com/content/11/1/243

Authors
Ciregia F, Giusti L, Da Valle Y, Donadio E, Consensi A, Giacomelli C, Sernissi F, Scarpellini P, Maggi F, Lucacchini A, Bazzichi L.
Journal
J Transl Med. 2013 Oct 2;11(1):243. [Epub ahead of print]

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.

 

[peggy-sue]

Folk might be interested in this info. from the paper, copied and pasted here.

"The patients were classified based on the 1994 Centers for Disease Control and Prevention CFS case definition [3]."

 

[LisaGoddard]

Thanks for posting this Joel. The scientific evidence for inflammation is really stacking up. I just which they would make some suggestions for treatment.

 

[Snow Leopard]

This is a study that made me go 'hmm!' a few times.

The study is based on a single pair of twins, but they have gone to a lot of effort, even to the point of the network analysis of the protein expression. They say it is a pilot study and to me it really sounds like they are planning on following it up with a larger study.

The study is limited also, because it is based on saliva only, rather than spinal fluid or blood serum.

Onto the interesting, they are studying a pair of men (unlike the last twin study that was all women), one of which developed CFS straight after a vaccination (something that I can sympathise with!).

They seem to make a big deal over upregulation of Cyclophilin A, as evidence of immune activation in response to viral infection, but interestingly, one of the roles of this enzyme is to actually supresses TNF-alpha, the also mention it is associated with Sjögren’s syndrome and Systemic sclerosis.

I was more interested in the downregulation of Zinc-alpha-2-glycoproteinas I am starting to lean towards a hypothesis of dysregulation of fatty acid metabolism* as the explanation for both fatigue, but particularly the kinetics involved, including PEM and the like.
This study claims that.

Considering that Russell and colleagues have demonstrated the ability of ZAG to reduce reactive oxygen species (ROS) production and to counter muscle atrophy associated with insulin resistance and other catabolic conditions [58], the decrease of ZAG that we found in WS seems to support the hypothetical role of oxidative stress in CFS.

The following study claims a few other features of ZAG. http://mcr.aacrjournals.org/content/6/6/892.long

Its expression is regulated by glucocorticoids. Due to its high sequence homology with lipid-mobilizing factor and high expression in cancer cachexia, it is considered as a novel adipokine. On the other hand, structural organization and fold is similar to MHC class I antigen-presenting molecule; hence, ZAG may have a role in the expression of the immune response. The function of ZAG under physiologic and cancerous conditions remains mysterious but is considered as a tumor biomarker for various carcinomas. There are several unrelated functions that are attributed to ZAG, such as RNase activity, regulation of melanin production, hindering tumor proliferation, and transport of nephritic by-products.

*All the obsevations from oxidative stress, decreased HSP, carnitine abnormalities, NO, and additionally, fatty acids and derivatives play key roles in the regulation of the immune system.

There is lots of potential here for altered regulation of the immune system into a dysfunctional steady state with effects on fatigue.

 

[August59]

Is the CFI / Lipkin study going to check saliva samples as well? It's not going to study it in the way these samples were studied though are they?

I sure wish they would, but a study seems to be set in stone. Just like Ungers ignorance to do a 1-day CPET study, instead of a 2-day study. That is just wasted money and in the end run is not going to mean anything to anybody that knows anything about this disease. All she has to do is look at Pacific Labs data and probably find out her answer without even carrying out her study. I don't know of anyone that failed a 2 day test at Pacific Labs that did not get their Social Security Disabilty approved.