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Rituximab target question

Discussion in 'Rituximab: News and Research' started by 62milestogojoe, Aug 13, 2017.

  1. 62milestogojoe

    62milestogojoe What's a forum then?

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    Hi, I'd be grateful if a member could tell me if the drug targets lymphoid progenitor cells.

    More specifically, does rituximab target B-cell precursors alone or both B cell precursors and lymphoid precursors.

    Thankso_O
     
  2. lansbergen

    lansbergen Senior Member

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    @Jonathan Edwards?
     
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  3. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Only pre-B cells. Even the earlier pro-B cells are not targeted. Haemopoietic stem cells are not affected so there is no effect on T or NK cell production as far as we know.
     
  4. neweimear

    neweimear Senior Member

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    @Jonathan Edwards if the ritux phase 3 trials are good, I will be trying to get treatment. My consultant is very wary of ritux, he says he has seen fatal outcomes of tb reactivation as a result of rituximab. So im not sure if he will ever prescribe it to me, he calls it a big gun drug. If he does not treat me, I will have to travel for treatment, I am saving money at present should that arise. My question is, is tb a possible outcome from ritux treatment? And secondly, would it be risky travelling for treatment as one would be going thru busy airports with a depleted immune system. Thanks so much for any thoughts on that.
    Also, I am interested on your thoughts on cyclophosphamide. We have nothing much to go on yet in terms of cyclo as a treatment for ME but in RA, can cyclo induce remission and how long of a remission would be standard? Would you see it as a possibility as a viable treatment for us if proved effective or too toxic and best avoided. Basically, is it a drug of last resort? Thanks.
     
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  5. Gingergrrl

    Gingergrrl Senior Member

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    Reactivation of TB and hepatitis are real risks with Ritux but if you have never had either in your lifetime (like me), then they cannot reactivate. PML can occur regardless but extremely rare. Please correct me, Dr. Edwards, if I got any of this wrong!
     
    ukxmrv likes this.
  6. 62milestogojoe

    62milestogojoe What's a forum then?

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    Thanks, I am attempting to reaquaint myself with neuro immunology vis a vis the interpretation of the PET scan ME study which I mentioned to you-
    http://forums.phoenixrising.me/inde...vidence-of-cognitive-dysfunction-in-me.53421/
     
  7. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I have never heard of rituximab reactivating TB in autoimmune patients. Does your consultant actually know what they are talking about? Reactivation of TB is a significant common problem with anti-TNF drugs like enabler and humour but rituximab has nothing to do with TNF inhibition. Maybe since I retired cases of TB have been reported with rituximab but for the first twelve years I worked on it iI never heard of a case.

    In general there is no risk in travelling if you have had rituximab. You might do well not to go to New Guinea but that's about it.

    Cyclo produces benefit in RA but it lasts about a month. So apart from dealing with life threaening crises, which are pretty much non-existent in RA now, it is useless. The toxicity is far too high. Bladder cancer is a major risk with long term repeated use. I understand the Norwegian physicians' interest in it but I would not want to use it.
     
  8. neweimear

    neweimear Senior Member

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    @Jonathan Edwards. Thanks for your replies, I cant wait to talk to my consultant! In relation to cyclo, why are Fluge and Mella using it if it does not bring long term benefit? I know they are trying it on severe patients now but if they only see benefit for a month, it seems strange. Would like to understand their reasoning for using it. Thanks again Jonathan.
     
  9. Snowdrop

    Snowdrop Rebel without a biscuit

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    Gingergrrl and neweimear like this.
  10. neweimear

    neweimear Senior Member

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    @Snowdrop I cannot download the file for some reason. Did you read it? If so, a very brief summary would be great, thank you!
     
  11. neweimear

    neweimear Senior Member

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    @Snowdrop...just googled it and found it, thanks very much :)
     
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  12. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Interesting at least in that they seem to have reviewed the literature and it still seems that TB is not a problem.
     
  13. 62milestogojoe

    62milestogojoe What's a forum then?

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    Clarification of rituximab action-differentiation between PRO and PRE cells

    [​IMG]

    Copyright 62milestogojoe 2017

    [​IMG]

    Copyright 62milestogojoe 2017 Rituximab targets CD20 protein on B cells. These are not present at the first stage of development or the last (plasma cell). Of interest perhaps---is that pre B cell receptor stage is still in the marrow. Does the B cell express CD20 at this stage in development or not until migration into the bloodstream as a naive B cell, or following progress to the secondary lymph nodes
    @Hip

    Resources used
    Immunology-Kuby, Freeman publications
    Medical immunology for students, Playfair and Lydyard, Chirchill Livingstone publications
    Immunolgy series on Youtube by Armando Hasudungen
     
    Last edited: Aug 15, 2017
  14. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Rituximab removes pre-B cells from marrow. It may actually have some impact on pro-B cells (from biopsies we did) but not on other lineages.
     
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  15. 62milestogojoe

    62milestogojoe What's a forum then?

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    So it does not begin from pro B phase and then increase?
     
  16. Gingergrrl

    Gingergrrl Senior Member

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    Thanks for your PM, Joe, and for posting your diagrams, which are very impressive, and I wish I had the ability to understand them!

    What is the difference between "pre-B cells" and "pro-B cells"? (in the most basic terms for dummies)
     
  17. 62milestogojoe

    62milestogojoe What's a forum then?

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    Hi, with regard to treatment with the drug I think Dr Edwards would be able to give you the best answer.

    From what I've understood from early pro to immature phases the development is antigen independent stage. From the naive stage on it becomes antigen dependent. I guess the important thing to note is that the drug is targeting cells within the bone marrow. I am a dummie too.
    Pre and pro simply means the cell hasn't matured into its final form.
     
  18. Gingergrrl

    Gingergrrl Senior Member

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    I don't think so :rolleyes:

    Are "pre" and "pro" B cells the same (meaning both simply have not yet matured into their final form) or do they differ? Also, which one comes first? I think from your diagram, the "pre" come first and are the precursor of everything that comes later?

    Are B cells, T cells, and NK cells the three types of WBC's that make up the immune system or are there others? This fascinates me but I still lack the basics. I would love to study this some how in the future if I get better.
     
  19. 62milestogojoe

    62milestogojoe What's a forum then?

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    Hi there are lots of others but I wanted to keep the diagram simple enough for everyone and couldn't fit much more on without it becoming a headbanger.:cry:

    GG just track the origin of the B cell sequentially through to its final form-the cell that produces antibodies. Your chemo drug will target B cells within the bone marrow. Rituximab is a :devil: to your B cells
     
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  20. Gingergrrl

    Gingergrrl Senior Member

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    Good and this is what I want b/c if I go into remission from Rituximab then it is proof that I have a B cell autoantibody driven disease (which is what my doctor is now calling it).
     
    62milestogojoe likes this.

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