Klimas: Plasma cytokines in women with chronic fatigue syndrome

[Smulan]

De Meirleir told me that IL-8 is often elevated in CFS/ME. Others have observed the same. This study indicates the opposite.

Chris

http://cfspatientadvocate.blogspot.com

Thats strange, perhaps IL-8 is not best cytokine to look at. In this study IL-8 has a fairly high spread so if the number of tested persons are low one could end up with the opposit result by chance.

 

[JillBohr]

Kim did post this study last month

You can find the link here:

http://forums.aboutmecfs.org/showthread.php?t=1081

This is a very interesting study.

 

[lisaxxx]

Cheney

Quote "Hasn't Dr. Cheney been saying there was a Th2 shift for like the past 10 years? "
The problem is that Cheney does not use any standard methodology
nor is any of his work peer reviewed nor has the results he reports been independtly reproduced.
This is one of the reasons that some say that what Cheney does actually retards the research for cure to CFS

 

[lisaxxx]

In the study

It says "Several studies report cytokine abnormalities in CFS; however, the findings are mixed. Differences between reports may be largely due to differences in methodologies"

I wonder if the results in This Study shows new and insightful information on CFS or if using yet another "different methodology " they have produced yet another "different result"

Jeez I need a simpler disease like say cancer

 

[Andrew]

I have a vipdx test that includes IL1B, IL2, IL4, IL6, IL8, IL10, and IL12.

Of these the elevated ones are:

IL6 is 128.8 (normal is <24 PG/mL) and
IL8 is 384.1 (normal is <14 PG/mL)

 

[leelaplay]

http://citeseerx.ist.psu.edu/viewdo...C03F?doi=10.1.1.94.5654&rep=rep1&type=url&i=0

Levi, you do come up with "good stuff, man."

This thesis, looking at gene expression data to predict ME/CFS, was in 2007. The author claims accuracy rates of 89% and 91% depending on methodology. Does anyone know if other follow-up work was done on this? Does this tie in with Dr. Kerr?

In this thesis, we show that CFS has a biological basis that is detectable in gene expression data better than blood prole and Single Nucleotide Polymorphism (SNP) data. Using random forests, the analysis of gene expression data achieves a prediction accuracy of approximately 89%. We also identify sets of dierentially expressed candidate genes that might contribute to CFS. We show that the integration of data spanning multiple levels of the biological scale might reveal further insights into the understanding of CFS. Using integrated data, we achieve a prediction accuracy of approximately 91%.

 

[acer2000]

Hmm I have high IL-8, but my other cytokines aren't consistently elevated. Weird...

 

[Dr. Yes]

The immune system is so unbe-LIEVABLY complicated and still poorly understood; one of the problems with any search for an ME/CFS biomarker within the cytokines is that they are expressed at different levels at different times, in response to different stimuli. IL-1, etc are large classes of interleukins that aren't specific for any one pathogenic mechanism or activation "phase".

What they could show, with more time-specific testing perhaps, is the presence of an inflammatory response to an infectious process of SOME kind. It wouldn't be a biomarker, but could be a smoking gun of sorts. But I think the best hope of finding an immune biomarker lies in first identifying pathogens involved in ME/CFS, then searching for patterns of immune activation uniquely related to them; the HHV-6 foundation has been trying to make inroads in this area, but has been short on funding since Reeves' CDC sought to sully the reputability of HHV-6 findings in ME/CFS after their "own" replication studies. (Where have we heard that before..)

 

[Dolphin]

Not sure if it has been pointed out that one can read the full paper for free at: http://www.translational-medicine.com/content/7/1/96

Table 1 has a nice table listing the 17 cytokines and saying their type (Pro-inflammatory, TH1, TH17, TH2, Anti-inflammatory and NK cell attracting). Maybe basic knowledge for some people but I lose track.

 

[Dolphin]

Make sure to check out extra file with the cut-off values for 5 cytokines

Its nice to see that this paper and dr Kerrs supporting something like a viral pathogen behind CFS

Take a look on IL-5. All PWCFS had higher levels then the controls. Perhaps IL-5 would be the most usefull for diagnostics?


.................... ME/CFS..................... Control...............................

Cytokin.......Med(low-high)............Med(low-high)..............average.

IL-5.. TH2...7.4 (6.3 - 10.0)...........3.8 (3.2 - 5.6)................+ 95

Yes, that is what they found:

"Applying (ROC) curve analyses, areas under the curves (AUC) for IL-5 (0. 84), LTα (0.77), IL-4 (0.77), IL-12 (0.76) indicated good biomarker potential."

However, you are not quite correct.

Values in parentheses are 25th and 75th percentiles.

If one goes to the file: [http://www.biomedcentral.com/content/supplementary/1479-5876-7-96-S1.doc], one can see the sensitivity and 1-specificity for the different values.
So one could take a result and if this data was correct, one can give the probabilities for the chances an individual does or does not have CFS.

 

[Dolphin]

Levi, you do come up with "good stuff, man."

This thesis, looking at gene expression data to predict ME/CFS, was in 2007. The author claims accuracy rates of 89% and 91% depending on methodology. Does anyone know if other follow-up work was done on this? Does this tie in with Dr. Kerr?

The study linked to was done using the empiric/Reeves criteria (see: 2.2 CAMDA dataset) so unfortunately I have little faith that they were studying CFS patients.

 

[Dolphin]

I don't have any direct evidence, but I think I go through "cytokine storms" at various times.

I'm not sure what triggers them, but I know they make me feel really bad.

It looks like they might produce one or more paper looking at this:

Obvious limitations of this study are that the samples represent
a single point in time and a single gender. The parent
protocol, from which the CFS samples were gathered,
is a larger longitudinal study. Subjects are followed over
18 months and sample collection includes times of relative
symptom remission or exacerbation. Completion of
the study will allow the correlation of CFS related symptoms
and other immune markers with the cytokine patterns.

 

[Hope123]

Having read a few papers on cytokines, the results are all over the place. Two interesting points from this paper, aside from those already pointed out:

1. Klimas et al. are very careful with their technique. There was a very short time (2hrs.) from blood draw to processing the cytokines simultaneously. According to cytokine
researchers I have talked to, a longer time to processing, which has happened in CFS studies, will skew results.

2. The samples were drawn at a designated time - in the morning - although we don't know exact times. My quick reading about cytokines makes me think that there are probably underlying circadian rhythms to them and taking cytokines at different times might give more disparate results so attempting to control somewhat for them is good.

I also wonder if they chose morning because at least for myself and some other people I've talked to, mornings can be brutal and I can feel even more flu-like than usual. There was a recent paper I've not yet read about FM and increase in nightime cytokines and I wonder if the increase carries over briefly into the morning.

 

[Andrew]

Conclusions: Cytokine abnormalities are common in CFS. In this study, 10 of 16 cytokines examined showed good to fair promise as biomarkers.

However, the cytokine changes observed are likely to more indicative of immune activation and inflammation, rather than specific for CFS. As such, they are targets for 3 therapeutic strategies.

I just reread this, and I"m wondering what those three therapeutic strategies are. Anyone know?

 

[jam338]

Cort, this statement about IL8 being lowered is confusing in contrast to this statement at http://aboutmecfs.org/blog/?p=969 :
"A Special Group of Patients - In this case Whittemore Peterson Institute was refreshingly direct in how they ’stacked their deck’. They stated the study participants had ’severe disability’, low natural killer cell functioning, increased pro-inflammatory cytokine levels (primarily IL-6, IL-8), .................

What am I missing??? Severe brain issues here.......IL-8 for me is over 4,000 when reference range should be <14

XMRV results pending through WPI clinical study via Gordon Medical Group, Santa Rosa.

I will never be able to find this thread again with my brain problems. Don't know how I found this now as it feels like I am surely dieing now... so if you can please email to jmclevis@aol.com.......thanks