A New Decade of ME Research: The 11th Invest in ME International ME Conference 2016
Mark Berry presents the first in a series of articles on the 11th Invest in ME International ME Conference in London ...
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Plasma cells as an innovative target in autoimmune disease with renal manifestations

Discussion in 'Other Health News and Research' started by Marky90, Mar 1, 2016.

  1. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    This seems like an intriguing article,
    Does anyone have access, so to give their verdict?
    I gather it`s relevant for us that treatments like rtx may not in a subset be effective against long lived plasma cells indirectly, and this has been discussed here before.

    "Autoantibodies are secreted by plasma cells and have an essential role in driving the renal manifestations of autoimmune diseases such as systemic lupus erythematosus and antineutrophil cytoplasmic autoantibody-associated vasculitis. Effective depletion of autoreactive plasma cells might be the key to curative treatment of these diseases. Two major plasma-cell compartments exist: short-lived plasmablasts or plasma cells, which result from differentiation of activated B cells, and long-lived plasma cells, which result from secondary immune responses. Long-lived plasma cells reside in survival niches in bone marrow and inflamed tissue and provide the basis of humoral memory and refractory autoimmune disease activity. Unlike short-lived plasmablasts, long-lived plasma cells do not respond to conventional immunosuppression or to therapies that target B cells. Existing therapies that target long-lived plasma cells, such as proteasome inhibitors and antithymocyte globulin, as well as promising approaches that target survival factors, cell homing or surface molecules, deplete the whole memory plasma cell pool, including cells that secrete protective antibodies. By contrast, we have developed a novel strategy that uses an affinity matrix to deplete pathogenic long-lived plasma cells in an autoantigen-specific manner without removing protective plasma cells. Targeting B-cell precursors to prevent replenishment of autoreactive long-lived plasma cells should also be considered."

    @Jonathan Edwards? :)

    http://www.nature.com/nrneph/journal/vaop/ncurrent/full/nrneph.2016.20.html
     
    Kati, Vasha, Justin30 and 4 others like this.
  2. msf

    msf Senior Member

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    Dunno if it´s included in the above group, but there is a trial of Rituximab in IgA Nephropathy going on at the moment.
     
  3. voner

    voner Senior Member

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    @Marky90,

    to acess the paper, go to http://www.sci-hub.io

    put the doi # (doi:10.1038/nrneph.2016.20) into the search field, and hit "return".....it may take a quite a while, but it will download..
     
    Last edited: Mar 1, 2016
    Kati and Marky90 like this.
  4. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Thanks a lot Voner!
     
    voner likes this.
  5. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    After reading the article I think we might be looking at something very essential for ME/CFS. Long lived plasma cells were not known of before 1997, and cyclo and rtx are ineffective in removing them!
     
    Justin30 and BurnA like this.
  6. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Just read this on wiki.. "Differentiation of mature B cells into plasma cells is dependent upon the transcription factors Blimp-1/PRDM1 and IRF4."

    Is it possible to target these transcription factors @Jonathan Edwards? Or will it cause too big of a hole in a persons immunity, as I seem to recall you have suggested before, when it comes to plasma cells.
     
  7. Jonathan Edwards

    Jonathan Edwards Senior Member

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    I am not sure there is much point in targeting the switching signals (transcription factors). Once the cells are plasma cells they are invisible to such targeting. If you remove b cells with rituximab there are no B cells to be switched. The problem is the mature plasma cells hiding away for years in bone marrow. There probably are ways to deplete them but at the moment there is very little political will in the science community to explore this - except perhaps from Andreas Radbruch's group. Still, it is useful to know all the pathways and it is just conceivable that blocking the plasma cell generation step would be a more easily reversible way to block continued plasma cell presence than continued rituximab usage.
     
  8. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Cool, gotccha!

    Is that group conducting any research now?

    And do you think it`s possible that some mechanism independent of B-cells, may keep those presumed dysfunctional long lived plasma cells (or maybe short lived as well), alive for longer than "usual"? (as far as i understand, there`s very little research on their longevity)

    I`m actually having another bone marrow biopsy in three months, when I have been approx 4 months on rituximab. I`ll ask them to have a look out for plasma cells and b-cells, to compare my biopsies. Could be interesting!
     
    Last edited: Jun 14, 2016
  9. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    As a side note,

    I`m perplexed as to why there`s a lack of political will to look into this. I mean, surely long lived plasma cell removal will be the holy grail for many known autoimmune diseases (such as Lupus), but probably also for some undiscovered ones. Of course the LPP`s when pathological, are part of a larger immune dysregulation, but they still must be dealt with somehow.

    There seems to be two approaches drug companies take before conducting research

    Either,

    1. Money on the table beforehand from the governement or others

    or

    2. Going all out on the basis of a reasonably well founded hypophesis

    I miss a scientific culture where the latter is the rule rather than the exception.
     
  10. wastwater

    wastwater Senior Member

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    IRF4 is of interest to me what happens if it's missing from the genes
     
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  11. eljefe19

    eljefe19

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    Can you expound on this a tad?
     
  12. wastwater

    wastwater Senior Member

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    Hi there I'll try
    I have a rare genetic disorder riegers syndrome and someone else who has it managed to get a whole genome scan,
    and only faults came back on chromosome 6,
    IRF4 was one gene that was mentioned Along with CCR6
    AS I think riegers syndrome,for some,maybe 20 percent,seems to come with an immune problem very much like ME/cfs with fibromyalgia being the most common diagnosis
    This is what raised my interest
    For completeness the other genes were HUS1B FOXQ1/F2 and C1 plus GMDS that has something to do with NADP+
     
    Last edited: Mar 17, 2017
  13. wastwater

    wastwater Senior Member

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    IRF4 is also called MUM1
    An article mentioning MUM1 and CFS which maybe of interest
    EBV-driven B cell lymphoproliferative disorders:from biology, classification and differential diagnosis to clinical management
    At www.nature.com
    Side note :CCR6 was an error
     
    Last edited: May 1, 2017
  14. wastwater

    wastwater Senior Member

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    IRF4 is interferon regulatory factor 4 (T helper cells th2 th17 th9 )
    GMDS is GDP-manose 4,6-dehydratase ,I think this can be involved in congenital disorders of glycosylation,im not sure what glycosylation is but have seen it mentioned on PR
    might be involved in glucose and carbohydrate use
     
    Last edited: May 6, 2017
  15. wastwater

    wastwater Senior Member

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    Leeds university have some papers on Irf4
     

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