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Peterson's biomarkers for rituximab responders?

Discussion in 'Rituximab: News and Research' started by jaybee00, Nov 26, 2016.

  1. jaybee00

    jaybee00

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    Hello,

    I read somewhere from Cort Johnson that Dr. Dan Peterson had found specific biomarkers that indicated which subset of patients would respond to rituximab. Does anyone know what these biomarkers/levels are?

    Thank you,

    JB
     
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  2. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I have not heard of this. I am not sure how anyone could know without having done a trial based on such possible markers. So far we are still waiting for a clear result from the main trial.
     
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  3. Cheesus

    Cheesus Senior Member

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    I think this may be what you're looking for:

    https://www.ncbi.nlm.nih.gov/pubmed/26399744
     
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  4. jaybee00

    jaybee00

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    sorry it was Patrick from UBC, not Peterson..my bad...see below

    1. #IACFS/ME #ME/CFS: Patrick - may eventually be able to identify which patients benefit fr Rituximab, need to test signature in larger study
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    2. [​IMG]Cort Johnson‏@CortJohnsonOct 28
      #IACFS/ME #ME/CFS - Patrick - Response signature DID NOT eliminate with treatment; Ritixumab does not eliminate all antibodies.
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    3. [​IMG]Cort Johnson‏@CortJohnsonOct 28
      #IACFS/ME #ME/CFS - Patrick - Rituxiamb responders using peptide assay, will upload to public data...
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    4. [​IMG]Cort Johnson‏@CortJohnsonOct 28
      #IACFS/ME #ME/CFS - Patrick - also searched for signature - 25 ME/CFS and healthy controls, easily able to differentiate responders from non
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    5. [​IMG]Cort Johnson‏@CortJohnsonOct 28
      #IACFS/ME #ME/CFS - Patrick - baseline and post-infusion plasma - Patrick is impressive speaker - rattlling fact after fact off
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    6. [​IMG]Cort Johnson‏@CortJohnsonOct 28
      #IACFS/ME #ME/CFS - Patrick - included bunch of other diseases - examined 18 responders and 7 non-responders to Rituximab, used baseline and
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    7. [​IMG]Cort Johnson‏@CortJohnsonOct 28
      #IACFS/ME #ME/CFS: Patrick - interrogated 125 and 130K peptides assess antibodies.From Univ British Columbia Complete Chronic Disease Study
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    8. [​IMG]Cort Johnson‏@CortJohnsonOct 28
      #IACFS/ME #ME/CFS - Patrick - talk about an international collaboration! (Patrick big wheel in BC medical circles.....)
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    9. [​IMG]Cort Johnson‏@CortJohnsonOct 28
      #IACFS/ME #ME/CFS - Patrick - BC Columbia - lists at least 30 researchers! Key collaborators UCSF, Workwell, Arizona State and Dr. Fluge/Mel
     
  5. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    My understanding is that things are complicated and so far we do not have a biomarker. Certain autoantibodies appear to be statistically significantly more common in ME patients than controls. However, this is a statistical difference in a population and it is not a very big difference in terms of what we would see in something like rheumatoid or lupus for instance. It is certainly not big enough to use as a diagnostic marker. Moreover, the antibodies are not in themselves markers of responsiveness from this.

    When it comes to the relation of autoantibody to response it does not seem necessarily that those with antibodies are more likely to respond. The people who are 'more likely to respond' are those who start with high antibodies and then show a lowering of antibody - but by that time they have already either responded or not and a response is a better marker of a response than something that might correlate with it!

    These findings are pointing in certain directions in terms of what mechanisms might be but I don't think they are anywhere near being response predictors. If they were it would be much easier to set up a trial looking specifically at this - what we have been searching for for about two years. The Norwegian/German collaboration may be further ahead than we know but I don't see a response marker out there yet.
     
  6. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I had a look at patrick's presentation at CMRC. It sounds as if he is hoping to find something but has not so far found anything. I am a bit sceptical of the blunderbuss approach to immunology there too, but you never know.

    What I found interesting about his presentation was that he emphasised how important it is to have population based cohort studies and he says that the UK have the best studies and Biobank in the world - which we probably do. And that is why I am unclear why the CMRC wants to ignore all the UK expertise and set up non-population based cohorts from clinic lists.
     
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  7. worldbackwards

    worldbackwards A unique snowflake

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    I'm not. :grumpy:
     
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  8. Cheesus

    Cheesus Senior Member

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    @Jonathan Edwards

    I am sure what you're saying is true. I just thought perhaps that study was the source of the misunderstanding as it suggests that those antibodies may be "biomarkers for response to B-cell depleting therapy".
     
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  9. RL_sparky

    RL_sparky Senior Member

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    Cort said the following on his board:
    "(Dr. Patrick in Canada believes he may have found a biomarker that will help identify which patients respond to Rituximab. Dr. Peterson is reportedly testing that biomarker in his patients. )"

    This quote is in the initial article under Rituximab update.
    http://www.healthrising.org/forums/...-plus-rituximab-and-new-drug-for-me-cfs.5004/
     
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  10. Hip

    Hip Senior Member

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    The above statement seems to suggest the reason some ME/CFS patients do not respond to rituximab is not because those non-responders have some non-autoimmune subtype of ME/CFS, but because for some reason, the rituximab did not work for these patients, and was not able to reduce the patients' production of autoantibodies.

    In other words, even in the rituximab non-responders, their ME/CFS may still be autoimmune in nature.

    That is not to say that the β2 and M4 autoantibodies are the cause of ME/CFS; ME/CFS may be caused by some other autoantibodies in the blood; but if rituximab is doing its job, it will reduce the level of all autoantibodies, so measuring the reduction in the β2 and M4 autoantibodies is just a gauge of whether rituximab is working.

    @Jonathan Edwards, am I on the right lines here?

    If the rituximab non-responders are indeed patients in which rituximab has failed to curb their autoimmunity, is there anything further that can be done in such cases? If these patients still have their ME/CFS caused by autoimmunity, can the autoimmunity be tackled in other ways if rituximab fails?

    And do we know why rituximab fails to reduce levels of autoantibodies in some patients?
     
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  11. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Yes, I think that is roughly right. There are several types of autoantibody that do not fall much with rituximab probably because they are made from long lived plasma cells. Even the autoantibodies that do go down do so to a varying degree from one person to another.

    I think the main problem with interpretation of all this is that the proportion of patients with autoantibodies is not that different to healthy people so they may not be relevant to the disease. One possibility we have considered is that the problem, at least for responders, is the presence of antibodies that are not auto- but are causing trouble for some other reason. If they are antibodies made by short lived plasma cells then there may be a response.
     
  12. Snow Leopard

    Snow Leopard Hibernating

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    [citation needed]

    I'd like to see Patrick from UBC's evidence on this.
     
  13. voner

    voner Senior Member

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    @Jonathan Edwards, that is intriguing, could you give some relevant examples of this?
     
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  14. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    There may be no well recognised diseases where antibodies cause trouble without being autoantibodies, except of course myeloma and Waldenstrom's macroglobulinaemia where the antibody is from a single clone and causes trouble through increasing blood viscosity. However, that does not mean there are none. There are various examples of the sort of thing that might cause problems, though. IgM antibodies are normally secreted as groups of five antibody molecules joined like the spokes of a wheel, but in some conditions, like RA, an increased proportion of IgMis secreted as single antibody molecules - monomeric IgM. In various autoimmune diseases antibody light chains are also produced on their own in increased amounts - so called free light chains. Normally every light chain is bound to a heavy chain and then to another chain pair to make a complete immunoglobulin. There are also variants of immunoglobulin that use unusual Vh region genes that are only produced under unusual circumstance. High levels of usage of Vh4-34 leads to haemolytic anaemia. None of these variations in antibody production may show up on an autoantibody test.

    Polymyalgia rheumatic is a common condition that is very likely due to misbehaving antibodies. Unusual antibody complexes have been found but nobody has ever found an autoantibody test positive. This is both common and very well understood in terms of inflammatory biology. The CRP goes way up, there is oedema around muscles and some patients have arteritis. It ought to be easy to find out what is causing it. However, nobody has a clue and it seems nobody is very interested - a bit like ME. PMR mostly affects the elderly and settles on steroids so nobody thinks it matters much. But it is a good example of a disease staring us in the face that nobody knows the cause of.
     

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