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Illness progression in chronic fatigue syndrome: a shifting immune baseline

worldbackwards

Senior Member
Messages
2,051
Don't think we've had this one yet.
  • Lindsey Russell†,
  • Gordon Broderick†
  • Renee Taylor,
  • Henrique Fernandes,
  • Jeanna Harvey,
  • Zachary Barnes,
  • AnneLiese Smylie,
  • Fanny Collado,
  • Elizabeth G. Balbin,
  • Ben Z. Katz,
  • Nancy G. Klimas and
  • Mary Ann Fletcher
†Contributed equally

Background

Validation of biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) across data sets has proven disappointing. As immune signature may be affected by many factors, our objective was to explore the shift in discriminatory cytokines across ME/CFS subjects separated by duration of illness.

Methods
Cytokine expression collected at rest across multiple studies for female ME/CFS subjects (i) 18 years or younger, ill for 2 years or less (n = 18), (ii) 18–50 years of age, ill for 7 years (n = 22), and (iii) age 50 years or older (n = 28), ill for 11 years on average. Control subjects were matched for age and body mass index (BMI). Data describing the levels of 16 cytokines using a chemiluminescent assay was used to support the identification of separate linear classification models for each subgroup. In order to isolate the effects of duration of illness alone, cytokines that changed significantly with age in the healthy control subjects were excluded a priori.

Results
Optimal selection of cytokines in each group resulted in subsets of IL-1α, 6, 8, 15 and TNFα. Common to any 2 of 3 groups were IL-1α, 6 and 8. Setting these 3 markers as a triple screen and adjusting their contribution according to illness duration sub-groups produced ME/CFS classification accuracies of 75–88 %. The contribution of IL-1α, higher in recently ill adolescent ME/CFS subjects was progressively less important with duration. While high levels of IL-8 screened positive for ME/CFS in the recently afflicted, the opposite was true for subjects ill for more than 2 years. Similarly, while low levels of IL-6 suggested early ME/CFS, the reverse was true in subjects over 18 years of age ill for more than 2 years.

Conclusions
These preliminary results suggest that IL-1α, 6 and 8 adjusted for illness duration may serve as robust biomarkers, independent of age, in screening for ME/CFS.
Full paper is here:
http://bmcimmunol.biomedcentral.com/articles/10.1186/s12865-016-0142-3
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
"Despite these differences in granularity and subgroup definition the subjects we studied in this work appear to display cytokine profiles similar to those found in the larger ME/CFS population studied by Hornig et al., [15]."

Nice.
 

A.B.

Senior Member
Messages
3,780
I don't really know but it does seem strange that the long term immune profile is that of exhaustion while simultaneously Rituximab appears to help about 1/2 to 2/3 of patients. Isn't the general belief that autoimmunity comes with increased immune activity? Will autoimmunity have to be redefined?
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
"One of the crucial effects of IL-6 is to promote b-lymphocyte maturation into plasma cells and enhance immunoglobulin production"

Well heellloo!

A.B: Maybe the apparant exhaustion is the immune system`s way of coping?
 

Jonathan Edwards

"Gibberish"
Messages
5,256
I don't really know but it does seem strange that the long term immune profile is that of exhaustion while simultaneously Rituximab appears to help about 1/2 to 2/3 of patients. Isn't the general belief that autoimmunity comes with increased immune activity? Will autoimmunity have to be redefined?

I don't think there has ever been a reason to think that autoimmunity arises from 'increased activity'. It is a state of inappropriate activity and in general a very specific inappropriate activity. I am not sure I recognise a concept of immune exhaustion in terms of cytokine levels. Attrition of T cells or bone marrow stem cells maybe, but I am not sure why that would have a specific cytokine signature.
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Ineresting that menopause affects the cytokine profile and the authors mention an association with apparent early menopause with ME/CFS. Anecdotally, my mother (who didn't have ME/CFS) complained to her GP fr many years about menopause like symptoms and was dismissed as 'too young'. After more than a decade of this she asked to be investigated for other conditions only to be told 'it's just the menopause'. Ahem!
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
I don't think there has ever been a reason to think that autoimmunity arises from 'increased activity'. It is a state of inappropriate activity and in general a very specific inappropriate activity. I am not sure I recognise a concept of immune exhaustion in terms of cytokine levels. Attrition of T cells or bone marrow stem cells maybe, but I am not sure why that would have a specific cytokine signature.

Thanks for claryfing this!
 

Jonathan Edwards

"Gibberish"
Messages
5,256
Low IL-6, high IL-8. I am actually beginning to believe this. This is the sort of routine basic replicative work that we need to do to get a foundation. If this pans out we can start speculating from a basis of a true 'signature'. The fact that it does not look like much else we have ever come across is all the better. Signs of inflammation get us nowhere. Signs of something unique are much more likely to.
 

Tuha

Senior Member
Messages
638
Low IL-6, high IL-8. I am actually beginning to believe this. This is the sort of routine basic replicative work that we need to do to get a foundation. If this pans out we can start speculating from a basis of a true 'signature'. The fact that it does not look like much else we have ever come across is all the better. Signs of inflammation get us nowhere. Signs of something unique are much more likely to.

I was a patient of KDM. I just checked the old tests which he did:
- IL-8S - 43,11 (0,00 - 15,00 pg/mL)
- IL-6S - 3,23 (0,00 - 5,00 pg/mL)
 
Messages
15,786
I was a patient of KDM. I just checked the old tests which he did:
- IL-8S - 43,11 (0,00 - 15,00 pg/mL)
- IL-6S - 3,23 (0,00 - 5,00 pg/mL)
From my first visit, after having ME for about 3 years:
IL-8 - 727 (0-15)
IL-6 - 4 (0-5)

After 2 years of treatment, my results from a few months ago (on a day where I had unusually bad swelling):
IL-8 - 465
IL-6 - 11
 

justy

Donate Advocate Demonstrate
Messages
5,524
Location
U.K
My IL8 was also high and remains so when tested as a patient of KDM - however I thought the abstract suggested it was high in patients ill less than 2 years, or have I missed something? I have been ill, to varying degrees or 20 years, but the last 7 has been severely. I was tested for IL8 6 years in to my severe relapse.

Anecdotally, my mother (who didn't have ME/CFS) complained to her GP fr many years about menopause like symptoms and was dismissed as 'too young'. After more than a decade of this she asked to be investigated for other conditions only to be told 'it's just the menopause'. Ahem!
This has been my exact experience also. Symptoms from age 35 told too young for menopause - this year at 46 told the same symptoms, which have still not been adequately investigated are just menopause. You honestly just cant win with the NHS can you?

Also told last week I have 'seen enough' specialists over the past 7 years, so it looks like I am now not allowed to develop any new issues :bang-head:. I have been recently diagnosed, by an NHS consultant, seen priavelty with MCAS, but am not allowed to now be seen by an immunologist on the NHS as I have seen 'enough consultants'.
 

mermaid

Senior Member
Messages
714
Location
UK
Ineresting that menopause affects the cytokine profile and the authors mention an association with apparent early menopause with ME/CFS. Anecdotally, my mother (who didn't have ME/CFS) complained to her GP fr many years about menopause like symptoms and was dismissed as 'too young'. After more than a decade of this she asked to be investigated for other conditions only to be told 'it's just the menopause'. Ahem!
Well, anecdotally again, my own ME symptoms came on gradually during my earlyish menopause. For around 4 years I put down my various symptoms to the menopause and believed that they would eventually improve. Sadly they didn't and when I acquired a 2nd autoimmune condition at 53 (the first one at 43) they began to slide further down. I am 63 now.
 

ghosalb

Senior Member
Messages
136
Location
upstate NY
From my first visit, after having ME for about 3 years:
IL-8 - 727 (0-15)
IL-6 - 4 (0-5)

After 2 years of treatment, my results from a few months ago (on a day where I had unusually bad swelling):
IL-8 - 465
IL-6 - 11
Hi Valentijn - after 2 years of treatment....do you feel better now ?