Thursday, 3 March 2016

ResearchSpeak: EBV creating myelin autoimmunity

How does IM trigger autoimmunity in people destined to develop MS? #ResearchSpeak #MSBlog #MSResearch

"The study below finds autoantibodies in people with infectious mononucleosus (IM), which are not found in normal controls. One autoantibody reacts to the myelin protein MOG (myelin oligodendrocyte glycoprotein). The authors suggest that the aberrant immune response that characterises IM may result in autoimmunity. This hypothesis is not new. However, it does not explain the long latency between IM and the clinical onset of MS. If autoantibodies are present as part of acute IM, why don't these people develop MS soon after their acute EBV infection? In addition, anti-MOG antibody response are not all the same and in general are very rare in typical MS. Anti-MOG responses are more common in children with inflammatory demyelination with a clinical picture that tends to mimic neuromyelitis optic, with very prominent spinal cord involvement. I do think this group is on the right track studying IM; we need to explain why people with IM are at increased risk of developing MS. This is one of the grand research challenges in MS. Any ideas would be welcome!"


Kakalacheva et al. Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein. Viruses. 2016 Feb 12;8(2). pii: E51. doi: 10.3390/v8020051

Background: A history of infectious mononucleosis (IM), symptomatic primary infection with the Epstein Barr virus, is associated with the development of autoimmune diseases and increases the risk to develop multiple sclerosis. Here, we hypothesized that immune activation during IM triggers autoreactive immune responses. 

Methods: Antibody responses towards cellular antigens using a HEp-2 based indirect immunofluorescence assay and native myelin oligodendrocyte glycoprotein (MOG) using a flow cytometry-based assay were determined in 35 patients with IM and in 23 control subjects. 

Results: We detected frequent immunoglobulin M (IgM) reactivity to vimentin, a major constituent of the intermediate filament family of proteins, in IM patients (27/35; 77%) but rarely in control subjects (2/23; 9%). IgG autoantibodies binding to HEp-2 cells were absent in both groups. In contrast, IgG responses to native MOG, present in up to 40% of children with inflammatory demyelinating diseases of the central nervous system (CNS), were detectable in 7/35 (20%) patients with IM but not in control subjects. Normalization of anti-vimentin IgM levels to increased total IgM concentrations during IM resulted in loss of significant differences for anti-vimentin IgM titers. Anti-MOG specific IgG responses were still detectable in a subset of three out of 35 patients with IM (9%), even after normalization to increased total IgG levels. Vimentin-specific IgM and MOG-specific IgG responses decreased following clinical resolution of acute IM symptoms. 

Conclusions: We conclude from our data that MOG-specific memory B cells are activated in subset of patients with IM.

18 comments:

  1. I keep thinking of MS as the hit and run theory.
    Those who get IM have their immune system compromised, then they recover to various degrees, some fully. Those that have not recovered fully have life events take place that lead to an immune system reaction such as ongoing chronic stress, injury, anxiety disorders, infections, hypoxia such as from sleep apnea, ongoing sleep deprivation leads to the body is unable to recover from stress and infections, plus others.
    A combination of these, then hitting a threshold lead to the white matter changes and hence MS signs and symptoms present themselves.

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  2. How do we know there is a gap between IM and developing MS?
    Do we just wait for clinical symptoms of MS to appear and then do tests? I was under the impression MS can be 'hidden' and doing damage without obvious symptoms. PWMS often say that looking back they had symptoms for years before dx.
    Are there studies following IM cases with MRI?
    I'm glad research is looking into IM.I had a very bad case 3 years before dx.I'm convinced it was a contributing factor.

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    1. I agree with that. In my humble opinion, MS could be lurking for a long time before it announces itself, perhaps through a spinal lesion, or yet another "hit" in the brain producing damage that cannot be circumvented. And when one is young, perhaps strong repair mechanisms can mask MS damage for a long time.

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    2. I tend to agree with both statements above i.e. chronic stress and MS being 'hidden' clinically but not immunologically.

      Also, is this zika virus not a good analogy? Many people get zika, acutely but they they recover. Others develop Guillain-Barre. Both had been infected with the virus but only in a subset of patients it manifests itself as neurological problems - sometimes months after, no?

      Also in the Guardian there was an article about the ebola case where people come back with neurological problems a year after the infection or so - check it out.

      Perhaps IM/EBV virus takes longer to manifest clinically? 5-10-20 years but it goes on in the body undetected and wrecks havoc?

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    3. Well, I had IM the first time in 2010. Then I had two relapses in 2013. For some unknown reason my immune system had an aberrant response to EBV and about 5 months after the last relapse early signs of MS appeared. I never had any other symptoms until the senses when the first outbreak. So, much so that I have only yet a spinal cord injury in the cervical (that was active at the time) and a small lesion in the brain, periventricular. I have always taken all vaccines, never had a problem of side effects for then. In my whole family (from grandparents to 4th cousins) I am the first case of MS... So who caused what, the immune system faced EBV form different or EBV did all this? ... If I had to attend for election for me to several studies about MS...

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  3. Perhaps a silly idea but it could be that specific viruses like EBV just hide better than other viruses and need more time to strike a long-term damage.

    I am thinking about shingles as well which can 'come out' 40 years after the first acute pox infection and become chronic.

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  4. I think it might be like the 1989 Batman movie that had Jack Nicholson as the joker. The poison wasn't in any one product but if you combined the wrong three products you were poisoned.

    Since we don't know any better we could assume it looks like this:

    Genetic susceptibility + EBV infection +( something else - vitamin D)

    I.e. Those that are genetically susceptible that are EBV positive are exposed to something else during a time when they are low on vitamin D.

    Could we model the above somehow? I don't think that is doable today.

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    1. I would tend to think that this 'something else' is stress and/or trauma.

      Stress tends to lower one's Vit D blood levels and if you don't replete Vit D because of lack of opportunity and time then all falls together and wham, MS outbreak??

      Could explain my case at least.......

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  5. To me the key is in understanding individual immune system responses to various possible triggers. We should be able to map a person's immune system - does it produce enough regulatory T-cells for instance? If not, why? I would like to believe that there is one trigger for all MS cases but I fear it's different for every patient and perhaps cumulative over time. I find it also true that MS can lurke in the background for years. I had my first flare when I was 36 but thinking back in time, the first time I felt something was wrong in my brain went back to when I was 21. And it was a less likely symptom - anxiety and paranoiac thoughts which came about after getting on the pill for the first time. Which makes me wonder if hormones have been looked into as a possible cause of destabilizing the immune system..

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    1. Never was on the pill yet got MS.

      But I've got an hormonal imbalance since teenage years so maybe??

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  6. To me the key is in understanding individual immune system responses to various possible triggers. We should be able to map a person's immune system - does it produce enough regulatory T-cells for instance? If not, why? I would like to believe that there is one trigger for all MS cases but I fear it's different for every patient and perhaps cumulative over time. I find it also true that MS can lurke in the background for years. I had my first flare when I was 36 but thinking back in time, the first time I felt something was wrong in my brain went back to when I was 21. And it was a less likely symptom - anxiety and paranoiac thoughts which came about after getting on the pill for the first time. Which makes me wonder if hormones have been looked into as a possible cause for destabilizing the immune system..

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  7. The ideas for the IM ratio explanation risk for MS, as mentioned above, and I have quoted here on Blog the outbreak of Zika virus and Chycungunia the onset of Guillain-Barré syndrome in affected individuals can give light to which follow exact path.
    Colombia and Brazil are fertile fields to such depth as the SGB numbers exploded in the two countries.
    A group of researchers in Rio de Janeiro realized that besides the SGB, the Microcephaly in fetuses, the ZV appears to cause brain damage in adults such as encephalitis and encephalomyelitis.
    I just wish that the Brazilian Government is truly join the international scientific community to expand the research.

    So what I mean is that they asks made on the Zika Virus and Chycungunia and their relationship with the nervous system and the immune system are very similar to those made on the possible interaction EBV - Immune System - Nervous System.

    You may also join forces and other areas researchers ideas, exemplifying the dutch molecular biologist Michael Pegtel who is conducting a very interesting study on whether there is a relationship of EBV, the Immune System and the Lupus....


    http://zorgkrant.zorgportaal.nl/index.php/bericht/8940-virus-zendt-lgeheimer-boodschap-tussen-menselijke-cellen.html

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    1. So is it that the EBV causes the autoimmunity regardless of the disease? The immortal B cell remembers, but the trigger is different between MS, Lupus etc.

      So EBV causes autoimmunity, not necessarily MS?

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    2. It also appears that EBV can cause autoimmunity, and it arises that the MS must interact with other factors (HERVs, genes, low vitamin D). The great thing is that all this needs to be proved. Unfortunately things happen in Biological Sciences "day to night" (except in the case of pandemics).

      So if the community about research and charitable MS don't unite in support of specific goals nothing will walk forward.
      Of course there must be several fronts of work, those who scour the possible causes, looking for treatment, etc. And I think that the contribution of specialists from other areas will add up and help you see ways not seen in MS research...

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    3. I think that EBV is everyone's worst enemy, people just don't realize it yet. If EBV is the worst virus in human history responsible for autoimmunity and numerous blood cancers; how can we make this virus public enemy number one?

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  8. I actually had IM when I was really young. MS was dx like 20 years after.
    Do we have an idea on the ratio between pwMS who had IM and those who didn't ?

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    1. Just had the answer reading your today's post :
      http://multiple-sclerosis-research.blogspot.com/2016/03/researchspeak-preventing-ms-by.html

      Thank you Dr. :)

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