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Article compares ME/MS and has a section on Rituximab

Discussion in 'General ME/CFS News' started by Adele, Nov 21, 2014.

  1. Adele

    Adele

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    http://www.biomedcentral.com/1741-7015/11/205. The article discusses MS/ME and points to lots of similarities between the diseases. It also discusses the use of Rituximab for both, and points to that Rituximab has shown effect in MS and also other neuroimmune diseases. Could this imply that Rituximab-treatment is more likely to be effective in ME-patients with autoimmune disease like MS in the family, as that may suggest that their ME is of the autoimmune subset? I know that many of the participants in the Rituximab-trial either had diagnosis of autoimmune disease themselves or in their first line relatives. Anyone else who wants to speculate? :)
     
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  2. Bob

    Bob

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  3. Adele

    Adele

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    Thank you for that Bob, and thank you for the link! :) Lots of new useful information there.
     
    Last edited: Nov 21, 2014
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  4. Jonathan Edwards

    Jonathan Edwards Senior Member

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    Welcome Adele. This is an interesting thought. I think I would say yes, we would expect that if rituximab does prove to be useful in ME, a family history of autoimmunity is likely to be at least a statistical indicator of response. It may not be a strong enough pointer to be helpful clinically but it would be worth investigating. Dr Fluge and Dr Mella were not able to find any clear pointers to likelihood of response in their first study but further studies may tell us that. Clearly finding indicators of response would be hugely useful in taking this sort of approach forward.

    I am not sure that I would expect the link to be particularly with MS. OK MS and ME both have some effect on the brain but that might not have anything to do with genetic risk factors. Some ME might go with a family history of lupus or some with thyroid disease or whatever. There is a suggestion that some ME might be linked to a DQ gene. The link did not look that strong but that again might be a subset issue.
     
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  5. Adele

    Adele

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    Thank you for your thoughts on that professor Edwards! And it will be very interesting to see if Fluge and Mella can find any links between these illnesses and a possible response to Rituximab in their further research. I know that if one has autoimmune disease in the family, or if one has one of those diseases oneself, then one will be more likely to develop an autoimmune disease, or another one. But are there also more specific links between the particular diseases? So that e.g. RA would predispose more for a specific of the other autoimmune diseases than the rest? Or do they seem to all mix together in a more random way? If there are patterns showing that some autoimmune diseases are more linked together than others, I guess it would be very interesting from a research point of view to know which ones are mostly linked to ME.
     
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  6. Jonathan Edwards

    Jonathan Edwards Senior Member

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    Yes, I agree, and yes there are specific connections. SO RA and MS are both associated with the gene DR4 (in simple terms) but most other autoimmune disease are not. DR3 has a weak link to several of the others. Lupus has very specific genetic links to complement genes not found in any other diseases. There is a rare genetic predisposition to multiple endocrine autoimmunities. So it's very complex. I have thought it would be good to do a large epidemiological study to see if this could be pinned down - maybe study all the 300,000 inhabitants of Iceland who all know their ancestors back to 900 AD, but maybe nobody gets ME in Iceland, and I guess it might take 3 million to do the stats!
     
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  7. Dr Speedy

    Dr Speedy

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    "but maybe nobody gets ME in Iceland",:

    Br Med J. May 21, 1977; 1(6072): 1350.PMCID: PMC1607215
    Icelandic disease (benign myalgic encephalomyelitis or Royal Free disease)A
    M Ramsay
    , E G Dowsett
    , J V Dadswell
    , W H Lyle
    , and J G Parish
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1607215/

    Icelandic ME Association
    ME FÉLAG ÍSLANDS

    View GalleryNameIcelandic ME Association
    Secretary GeneralEyrún Sigrúnardóttir
    Web Addresshttp://www.mefelag.is/

    Contactmefelag@gmail.com


    The Icelandic ME Association was founded on March 12, 2011.
    http://www.euro-me.org/Icelandic ME association.htm
     
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  8. lansbergen

    lansbergen Senior Member

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  9. Jonathan Edwards

    Jonathan Edwards Senior Member

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    So maybe Iceland would be a good place to do a study after all.
     
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  10. Snow Leopard

    Snow Leopard Hibernating

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    A side issue, but there was a more recent Icelandic population based study too:

    The prevalence of chronic fatigue syndrome in Iceland - a national comparison by gender drawing on four different criteria. (2002)
    http://www.ncbi.nlm.nih.gov/pubmed/12470318
     
  11. Dr Speedy

    Dr Speedy

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    "The study was carried out to estimate the prevalence of chronic fatigue syndrome (CFS) in Iceland. No previous prevalence studies known to us have been undertaken in Iceland or in Scandinavia. A 95-item custom-made questionnaire was sent to 4000 randomly selected people. The response rate was 63%."

    "Women were in a majority (78%); their mean age was 44, they were fully employed and worked long hours. They believed that the onset of their symptoms was stress related. The type of work was unskilled in the majority of cases."

    "Men had more frequently phobic symptoms (P < 0.001) than did women. Differences were found in the prevalence of phobia and panic (P < 0.001) between women in the CFS group compared to healthy ones. A positive correlation was found in the prevalence of phobia between women in the CFS group and those with Iceland Disease."

    Thx SNOW LEOPARD but What a load of CRAP from these psychos !!!
     
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  12. Jonathan Edwards

    Jonathan Edwards Senior Member

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    Yes, I noted that in Iceland CFS is different from REAL Iceland disease. The genetics may be there but ...
     
  13. Marco

    Marco Grrrrrrr!

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  14. Jonathan Edwards

    Jonathan Edwards Senior Member

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    It would be in contrast to virtually all common autoimmune conditions. There is a suggestion that MS may show changes in rates in populations consistent with the arrival of infection like measles but this does not look at all like a standard epidemic and is open to various interpretations. Otherwise autoimmune diseases are not epidemic.

    Nevertheless, there is nothing to say that there is no exception to this. Coeliac disease is an exception in that its T cell response is to a food component. Certain forms of autoimmune arthritis are exceptions in occurring only in children - etc etc. There is room for all sorts of exceptions within any theory of autoimmunity I think. And of course these may not be the autoimmune ones - that may be some others.
     
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  15. Marco

    Marco Grrrrrrr!

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    Thanks for the clarification (or 'muddification').;)

    ETA - I'm still not convinced that the rates/geographic clustering stack up though even if an environmental factor is a possibility
     
    Last edited: Nov 27, 2014
  16. Woolie

    Woolie Senior Member

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    @Jonathan Edwards On the question of autoimmunity in ME, I'm puzzled by one thing. I simply don't understand why the success for rituximab would necessarily support an autoimmune hypothesis. As I understand it, one account of ME, especially post-infective ME, thats still be given serious consideration, is poor maintenance of herpesvirus latency in B cells (whether due to depleted EBV CD8+ or CB4+ T cells or whatever) So by this account, destroying B cells would presumably kill a large population of latently infected cells, so lead to temporary - and maybe longer - relief.

    What am I missing?
     
  17. Jonathan Edwards

    Jonathan Edwards Senior Member

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    In fact I have mentioned this on several threads but it is an issue of detailed evidence: subtle, but detail is crucial in understanding these things.

    The reason why we think rituximab is working in autoimmune disease by an effect on antibody production rather than some knock on effect on other processes is the shape of the response curve. Improvement in RA, for instance, develops gradually over a period of 3-6 months. That can be tracked very accurately with C reactive protein levels going down and the fall is a long slow smooth curve. It takes much too long to be explained just by removal of early or midlife B cells. If you then track autoantibody levels - which my lab has been doing week in week out for fifteen years - you find the curve fits the improvement curve very well. It takes 3-6 months for the antibodies to decline because that depends on mature plasma cells dying off.

    When rituximab was used in ME Dr Fluge and Dr Mella, who are oncologists, were no fully aware of the time course of improvement seen in autoimmune diseases. Their own disease, lymphoma, gets better very quickly because improvement is just due to the removal of the malignant b cells, which takes hours or at most a few days. So they were surprised to see that it took 3-6 months for the patients to improve until I was asked to comment on their paper and pointed out that the time course is exactly right for autoimmunity.

    If rituximab was working by removing B cells full of EBV improvement should not take more than six weeks at the very most and I would expect it to be no more than three weeks. There is no reason why, if virus is removed today, that it should be producing symptoms in several weeks time. Usually when the body makes an effective immune response to EBV symptoms settle within a week or two. So the pattern of improvement with rituximab really makes no sense in terms of removing EBV.

    What might be true is that EBV is necessary for a disordered autoimmune or autoinflammatory process to persist. So it might be that you will only get long term remission if you also clear away EBV. In fact this does not fit very well either since rituximab is very good at removing EBV and a lot of patients relapsed after improving - so again it does not seem to fit with continued presence of EBV being involved.
     
    Last edited: Dec 2, 2014
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  18. Jonathan Edwards

    Jonathan Edwards Senior Member

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    Another point to note is that about half of the Norwegian patients seemed to respond. Taking into account the fact that no disease shows 100% response that would suggest that a majority of patients have a rituximab sensitive illness. If that was due to reactivated EBV I think Dr Scheibenbogen would have found more uniform EBV response abnormalities. As it is Dr Scheibenbogen has found differences in antibody responses in a minority, as I understand it. Dr Hornig was unable to find evidence of increased virus. So if EBV reactivation is involved in ME it looks as if it is likely to be a minority. And the other herpes viruses would not be affected by rituximab because they do not live in B cells like EBV.

    The presence of EBV may still be more generally relevant, but it looks to me as if it will be in a much more indirect way.
     
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  19. Helen

    Helen Senior Member

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    I found this interesting article in the Swedish journal for doctors, Läkartidningen, by a doctor diagnosed with ALS. Maybe it can add something to this thread (@Jonathan Edwards ?).

    http://www.lakartidningen.se/Opinion/Debatt/2014/11/Fran-off-pistakning-till-rullstol-pa-15-ar/

    When he got sick he researched Rituximab in MS a. o. at the Karolinska Institute in Stockholm. He found that he had increased B-cells himself, and tried treatment with Rituximab. To make his story very short he is convinced that the treatment has prolonged his life. His findings will be published later. I hope that though you will need a google translation the article will be worth reading.
     
  20. A.B.

    A.B. Senior Member

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    Is an increased number of B lymphocytes typical for diseases that respond to Rituximab? If so, how is "increased" defined? My B lymphocytes were 17% of the lymphocyte population, with a normal range being 2-18.

    Edit: since I'm at it: NK lymphocytes were 31% with a range of 2-30, and T lymphocytes were decreased at 49% with a range of 55-86.
     

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