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The role of Adaptive and Innate immune cells in Chronic Fatigue Syndrome/Myalgic Enchephalomyelitis

Discussion in 'Latest ME/CFS Research' started by aimossy, Dec 19, 2013.

  1. aimossy

    aimossy Senior Member

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    Last edited: Dec 19, 2013
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  2. alex3619

    alex3619 Senior Member

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    The Role of Adaptive and Innate Immune Cells in Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis

    Ekua Weba Brenu1,2,*, Teilah K. Huth2, Sharni L. Hardcastle2, Kirsty Fuller2, Manprit Kaur2, Samantha Johnston2, Sandra B. Ramos2, Don R. Staines2,3 and Sonya M. Marshall-Gradisnik1,2

    School of Medical Science, Griffith University, Gold Coast, Australia
    The National Centre for Neuroimmunology and Emerging Diseases, Griffith Health Institute, Griffith University, Gold Coast, Australia
    Queensland Health, Gold Coast Public Health Unit, Robina, Australia

    *Corresponding author: Ekua Brenu Contact email: e.brenu{at}griffith.edu.au Griffith University, Medical Science, 16 High Street, 16 High Street, Southport, Queensland, Australia, 4215, Phone: +61 7 5678 9282

    Received June 23, 2013.

    Int. Immunol. (2013) doi: 10.1093/intimm/dxt068 First published online: December 16, 2013


    Abstract

    Perturbations in immune processes are a hallmark of a number of autoimmune and inflammatory disorders. Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME) is an inflammatory disorder with possible autoimmune correlates, characterised by reduced Natural Killer (NK) cell activity, elevations in regulatory T cells (Tregs) and dysregulation in cytokine levels. The purpose of this paper is to examine innate and adaptive immune cell phenotypes and functional characteristics that have not been previously examined in CFS/ME patients. 30 patients with CFS/ME and 25 non-fatigued controls were recruited for this study. Whole blood samples were collected from all participants for the assessment of cell phenotypes, functional properties, receptors, adhesion molecules, antigens and intracellular proteins using flow cytometric protocols. The cells investigated included NK cells, dendritic cells (DCs), neutrophils, B cells, T cells, γδT cells and Tregs. Significant changes were observed in B cell subsets, Tregs, CD4+CD73+CD39+ T cells, cytotoxic activity, granzyme B, neutrophil antigens, TNF-α and IFN-γ in the CFS/ME patients in comparison to the non-fatigued controls. Alterations in B cells, Tregs, NK cells and neutrophils suggest significant impairments in immune regulation in CFS/ME and these may have similarities to a number of autoimmune disorders.

    Key words B cells γδT cells Dendritic cells NK cells Degranulation
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  3. Firestormm

    Firestormm Guest

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    And next we need/I need a translation....! :wide-eyed:
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  4. alex3619

    alex3619 Senior Member

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    To really translate requires the full paper. I am however considering going to the authors to see if I can get a comment. Its a local phone call for me and we have the email.

    A very superficial translation is they looked at a whole stack of immune factors, and found issues with B cells, regulatory T cell, Natural Killer cells, and neutrophils.

    It would be interesting to see if the B cell issues have any implications for Rituximab.

    The rest depends on the details. Given that they have just called for healthy controls for a new study to look into markers, I am hoping that this new study might give us a diagnostic blood test.
    Last edited: Dec 19, 2013
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  5. Firestormm

    Firestormm Guest

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    Thanks Alex. If you think it's worth writing it up into an article I can lend a hand. Though for this single study, perhaps a thread summary might work as well :)
  6. aimossy

    aimossy Senior Member

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    Thanks Alex and Firestormm.:D
    I am so keen to see the full article!
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  7. lansbergen

    lansbergen Senior Member

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  8. alex3619

    alex3619 Senior Member

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  9. alex3619

    alex3619 Senior Member

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    Do keep in mind that this is probably a similar study to what Cort wrote about here:

    http://simmaronresearch.com/2013/12...research-definition-chronic-fatigue-syndrome/

    I don't think its the same study, but I am not entirely sure. The reason I think its not the same study is that there is no mention of ICC or Fukuda in the abstract for the study in this thread. The numbers of people enrolled are also different.
    Last edited: Dec 19, 2013
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  10. lansbergen

    lansbergen Senior Member

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  11. Legendrew

    Legendrew Content team

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    With such a vast array of dysfunction and deficits present in different immune populations i'd be very intrigued to see how the cytokine levels are - my guess would be that there is a whole host of cytokines being thrown around in response to this dysfunction, keeping the undeniably damaging loops going. It certain fits with the dysfunctional immune status of other autoimmune conditions and perhaps even surpasses the dysfunction seen in certain autoimmune conditions. I hope we can see a little more of the paper at some point.
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  12. alex3619

    alex3619 Senior Member

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    @Legendrew, the new Lipkin paper will (according to his press release a couple of months ago) show that the blood cytokines are highly variable, but spinal fluid cytokines show a marked pattern. Its one of the papers I am highly anticipating, as is further release of data from NCNED, the results of the Rituximab phase 2 trials, and the independent replication of the 2 day CPET.
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  13. alex3619

    alex3619 Senior Member

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    I just sent an email to Ekua Brenu, the contact person for the paper. I hope to hear something in reply, but given its close to Christmas I am not expecting anything promptly.
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  14. cigana

    cigana Senior Member

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    pm me if you need this paper (I have already sent to alex and aimossy)
  15. cigana

    cigana Senior Member

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  16. alex3619

    alex3619 Senior Member

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    Interesting stuff .. my eyes keep glazing over though, I can't concentrate for long. However there is stuff in here that is not implied in the abstract, and I hope to make a few comments in the next several days.
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  17. taniaaust1

    taniaaust1 Senior Member

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    Looking forward to reading your comments alex. I cant currently get my brain around the immune stuff
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  18. bambi

    bambi

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  19. alex3619

    alex3619 Senior Member

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    The Role of Adaptive and Innate Immune Cells in Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis

    30 Fukuda diagnosed CFS patients and 25 controls were studied. Their disease duration was kind of short at over 2 years, which might imply (based on Lipkin's unpublished findings) that they were a CFS subgroup, the under 3 year group.

    Numbers of classes of immune cells were normal, but numbers of subtypes were not normal for dendritic cells and B cells. pDCs were decreased (I think they mean plasmacytoid dendritic cells), and immature B cells were decreased, with memory B cells increased.

    This finding of low immature B cells is interesting, and contradicts earlier findings of more immature B cells. I wonder if this is related to the putative 3 year transition stage between short term and long term patients?

    An increase in memory cells might mean the body is fighting something. This implies pathogens or toxins, autoimmune or autoinflammatory processes.

    This profile of B cells is consistent with an autoimmune disease.

    Plasmacytoid cells release interferons (mainly alpha and beta interferon), so a decrease might mean reduced resistance to viruses. HIV infection decreases their numbers, so its possible a range of B cell infections can do this.

    Regulatory T cell numbers were high including one subtype. This might mean the body is trying to suppress the immune response especially in autoimmune disease. Their capacity for producing adenosine is also higher.

    Adenosine can cause vasodilation (and therefore might be implicated in orthostatic intolerance), bronchospasm (one of my symptoms), with possible effects on phosphodiesterases. This last is interesting, because it might make proper sleep very very difficult, something I have blogged on. However it might also make people sleepy and possibly help initiate sleep. So if its high it might be that you can kind of get to sleep but not sleep very well. More importantly for us the more adenosine you have the more tired you will be. Caffeine can counteract adenosine function, but I think resveratrol might too (by implication, not proven science). These two agents might even improve blood flow, again by implication not proven science. However the adenosine might have antiinflammatory effects, so blocking it might increase inflammation.

    Natural killer cell function was down when tested. This is in line with many other studies. However numbers of interferon gamma NK cells were increased. Interferon gamma targets viral and intracellular pathogens, and cancer cells. I wonder if this explains why with lower NK function we do not appear to have higher incidence of cancer except for lymphomas, which are either B or T cell cancers?

    At a chemical level they found increased interferon gamma with the NK cells, supporting the finding that interferon gamma producing NK cells were increased.

    Granzyme B was significantly decreased. This enzyme cuts proteins and is used to target virally infected cells and induce cell death. A decrease in this might mean we cannot clear viral infections properly.

    Various factors were found to positively and negatively correlate with each other. This is complex to explain (and would require more research from me than I have time for) so I will just comment on the negative correlation between Tregs and NK cell cytotoxic function. This might imply, together with other research, that our high Tregs might be suppressing our NK cells. Which begs the question, why are our Tregs high? Is this autoimmune or autoinflammatory?

    There is also something wrong with the binding of antigens to neutrophils. I don't know enough about this to be sure, but its likely that it means neutropils cannot properly bind to cells that should be targeted by the immune system. Since neutrophils can be up to 80% of our white blood cells this is concerning. Neutrophils are involved in chronic inflammatory conditions, but I am unsure just what this finding implies.

    Neutophil function is discussed here: http://medicine.cf.ac.uk/molecular-...ing/neutrophil-resources/neutrophil-function/

    Be warned the article in the link is a little technical. What I think the low antigen binding in CFS might mean is that yet again our immune system cannot kill problem cells effectively.

    Having most of our innate immune system less functional, and our adaptive immune system possibly dysfunctional in various ways, might imply we have major problems in our immune system. What a surprise!

    The paper sums it up this way:

    They are not specific about results, but alterations in platelets and sedimentation rates are implied to be increases in patients. So we might have an increased tendency to blood clotting and failure in microcirculation, which fits with much earlier findings in CFS of problems with blood flow and increased clotting that were treated with heparin.

    I find it fascinating how this study might explain so many of our problems, from chronic infection and chronic inflammation, to excessive tiredness and disrupted sleep. As usual this just begs more research, but how is this done with limited funding?

    The paper ends with this:

    Last edited: Dec 25, 2013
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  20. alex3619

    alex3619 Senior Member

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    PS. Just thinking about all this, we have vasodilation and blood clotting? What in Hades does that combination do?

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