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Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome

Discussion in 'Latest ME/CFS Research' started by Ecoclimber, Jan 16, 2014.

  1. Ecoclimber

    Ecoclimber Senior Member

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    Mercer Island Wa
    Full Text Article:
    http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085387

    Deficient EBV-Specific B- and T-Cell Response in Patients with Chronic Fatigue Syndrome

    Madlen Loebel equal contributor *, Kristin Strohschein equal contributor, Carolin Giannini, Uwe Koelsch, Sandra Bauer, Cornelia Doebis, Sybill Thomas, Nadine Unterwalder, Volker von Baehr, Petra Reinke, Michael Knops, Leif G. Hanitsch, Christian Meisel, Hans-Dieter Volk, Carmen Scheibenbogen

    Published: January 15, 2014
    DOI: 10.1371/journal.pone.0085387

    Abstract

    Epstein-Barr virus (EBV) has long been discussed as a possible cause or trigger of Chronic Fatigue Syndrome (CFS).

    In a subset of patients the disease starts with infectious mononucleosis and both enhanced anddiminished EBV-specific antibody titers have been reported.

    In this study, we comprehensively analyzed the EBV-specific memory B- and T-cell response in patients with CFS. While we observed no difference in viral capsid antigen (VCA)-IgG antibodies, EBV nuclear antigen (EBNA)-IgG titers were low or absent in 10% of CFS patients.

    Remarkably, when analyzing the EBV-specific memory B-cell reservoir in vitro a diminished or absent number of EBNA-1- and VCA-antibody secreting cells was found in up to 76% of patients.

    Moreover, the ex vivo EBV-induced secretion of TNF-α and IFN-γ was significantly lower in patients. Multicolor flow cytometry revealed that the frequencies of EBNA-1-specific triple TNF-α/IFN-γ/IL-2 producing CD4+ and CD8+T-cell subsets were significantly diminished whereas no difference could be detected for HCMV-specific T-cell responses.

    When comparing EBV load in blood immune cells, we found more frequently EBER-DNA but not BZLF-1 RNA in CFS patients compared to healthy controls suggesting more frequent latent replication.

    Taken together, our findings give evidence for a deficient EBV-specific B- and T-cell memory response inCFS patients and suggest an impaired ability to control early steps of EBV reactivation.

    In addition the diminished EBV response might be suitable to develop diagnostic marker in CFS.


    Eco
    merylg, Simon, MeSci and 15 others like this.
  2. shannah

    shannah Senior Member

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    You've been busy posting some really good research today Eco. This one's out of Germany.
    merylg, MeSci and rosie26 like this.
  3. anciendaze

    anciendaze Senior Member

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    This paper looks like the real thing. The immune impairment they describe is highly specific to EBV. One of the surprises in the main text is that none of the CFS patients they tested with a challenge involving a polypeptide from EBNA-1 produced an IFN-gamma response. This fits perfectly with the hypothesis of latent replication. Their results concerning deficits of polyfunctional immune cells with three different functions helps explain earlier mixed results concerning EBV. Researchers were looking for much less specific immune impairment.
    merylg, Simon, MeSci and 6 others like this.
  4. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    I wonder if this may explain those of us who have had cfs/mono and had igm/igg antibodies later test negative to these so called life long igg antibodies? ?
    merylg and snowathlete like this.
  5. beaverfury

    beaverfury beaverfury

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    Could this explain some of the success of Rituximab ? EBV is latent in B cells isn't it?
    merylg and snowathlete like this.
  6. snowathlete

    snowathlete

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    Very interesting. Could be massive. Hope someone is up to writing an article on this explaining it more.

    I had an NHS test for EBV IgG which came back positive but then another test elsewhere came back negative a year later. Perhaps the tests were looking at different antigens; the second looking for the one above? And not finding it.

    I had terrible mono as a teen.
    merylg and heapsreal like this.
  7. beaverfury

    beaverfury beaverfury

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    Could join a lot of dots up....

    Not great for treatment options though. Antivirals seem to bounce off EBV.

    Here's an article where they used Stem cell transplants for Chronic Activated EBV. (Pg 4)
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776035/#!po=38.8889
    merylg and Ema like this.
  8. alex3619

    alex3619 Senior Member

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    One word: yes.
    merylg, Simon, MeSci and 2 others like this.
  9. alex3619

    alex3619 Senior Member

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    I have been saying for some time now that we need a good evoked response test. Fibroymyalgia has one with abnormal cytokines, now we have our own version. We also have, of course, the 2 day CPET, excercise challenge and muscle fiber induced problems. It is likely that those with ME, and many currently diagnosed with CFS (but not all) will show the immune problem in this paper, in which we cannot effectively fight EBV. However the study used Fukuda, I am still thinking about the implications of that.

    I hope to summarize this paper but I am very busy at the moment, so it might be quite a while if at all. It does need to be replicated, and further studies will be required. However this model again fits many divergent explanations and observations. Is possible its wrong, or misleading (more pathophysiology but not causation), but currently its looking very good indeed.
    merylg, MeSci and snowathlete like this.
  10. snowathlete

    snowathlete

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    They might be able to provide us the same immunity as everyone else by cloning the right antibody as a biological product perhaps. Though that would be expensive i suspect and might require constant repeat doses. Perhaps it might work in unison with Rituximab.
  11. A.B.

    A.B. Senior Member

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    This looks promising. We might get a reliable biomarker out of this work, which would be a big step forward.
    merylg and MeSci like this.
  12. Gijs

    Gijs Senior Member

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    Don't forget that EBV will reactivated by (chronic) stress(respons) mental and physical. This can explain PEM. It works both ways.
    merylg and Jon_Tradicionali like this.
  13. Soundthealarm21

    Soundthealarm21 Senior Member

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    This study only helps those people with EBV (I am one of them, started with mono, still have high titers), but it does not account for people with say CMV, HHV6, Parvo B19, etc. IMHO, this could be a biomarker for a subset which would be great, but Big Pharma will start to target a specific issue and it will lead to more symptom based treatment.

    Would it be good to be able to knock out EBV? Yes, absolutely. But that is only a small part of the overall picture when there is obviously much more than EBV wrong with people.
  14. Gijs

    Gijs Senior Member

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    This is not entirely true. Because NK cel disfunction which is consistently found in ME patiënts can be the key problem in controlling virusses as CMV, HHV^6....(CO infections) NK cel dysfunction can be caused by this specific chronic latent EBV infection. It could be the cause of everything. Time will tell us. However it is a very important finding which could lead to more research and a breakthrough. It makes sense.
    Antares in NYC, Iquitos and RL_sparky like this.
  15. alex3619

    alex3619 Senior Member

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    Less than one percent of adults do not have EBV. This model is not about the titres, and probably not about acute viremia. Hence serum titres may not be important.

    However if we have this problem with one virus, how about others, especially the herpes and enterviral familes?

    Further, its also possible our NK problems are secondary to something here. We just don't know yet. You can bet the NK researchers are now thinking about this. It would be interesting to read their thoughts on it.

    Its important to emphasize that the EBV problems in this study appear to have little to do with NK issues, thats another layer, though its also possible that without a working NK capacity the response to EBV might be attenuated due to prolonged insufficient activation of the immune system.
  16. Daffodil

    Daffodil Senior Member

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    i would agree that the picture is a lot more complex because antivirals don't help all of us..maybe not even most of us.

    antivirals should help even if we are not making antibodies
  17. Marco

    Marco Old blackguard

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    Quite interesting.

    Perhaps Prof Edwards could give us his assessment given the autoimmunity links?
    Kati and MeSci like this.
  18. Waverunner

    Waverunner Senior Member

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    Very interesting finding. If EBV is the cause, we have to ask ourselves, why Valtrex is no solution to this problem. Shouldn't we have found out by now?
  19. rosie26

    rosie26 Senior Member

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    Just looked at my labs and I am negative for EBV past or present.
  20. Valentijn

    Valentijn Activity Level: 3

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    Same here for tests from a lab I don't completely trust - thought it might be due to my immune system being buggered. I'll have more thorough results in week or so, from a better lab.
    merylg and rosie26 like this.

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