The 12th Invest in ME Conference, Part 1
OverTheHills presents the first article in a series of three about the recent 12th Invest In ME international Conference (IIMEC12) in London.
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B cells remain in the brain after rituximab treatment (MS Research)

Discussion in 'Rituximab: News and Research' started by ukxmrv, Apr 27, 2017.

  1. ukxmrv

    ukxmrv Senior Member

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    341 Persistent B lymphocytes in multiple sclerosis plaques after rituximab treatment S. esfandi (University of Colorado), S. Salimian (U of Colorado School of Medicine), J. Corboy (U of Colorado School of Medicine), E. Alvarez (University of Colorado).

    To describe the persistence of inflammation lymphocytic infiltrates in plaques from a postmortem case of aggressive multiple sclerosis (MS) after treatment with Rituximab.

    Background: B-cells are believed to be strong autoimmune effector cells in the pathogenesis of MS. Rituximab depletes B-cells in the peripheral blood and is an effective treatment for MS. However, this effect may not extend to the CNS as effectively. Spinal fluid analysis from multiple studies has shown the persistent presence of B-cells after rituximab treatment, despite elimination from peripheral blood.
    Design/Methods: Case report. Results: 30 year old man with aggressive multiple sclerosis was diagnosed in 2010 and presented to University of Colorado in 10/2013 in a wheelchair. He was treated with Tysabri from 10/2013 until 8/2014. He was JCV+ and was then treated with 1 gram of rituximab in 9/29/14. He was showing gradual improvement and was beginning to ambulate with a walker (leg strength went from 2/5 to 4/5) when he died on 1 November15. He had received two additional 500mg doses with the last dose on 15 September. His peripheral CD19/20 counts stayed undetectable. His last MRI Brain on 3 July 2015 was stable.

    CNS autopsy verified severe multifocal brainstem and cerebral periventricular white matter plaque burden. Microscopically, several plaques manifested conspicuous perivascular lymphocytic cuffs, predominantly CD3+ T cells (mixed CD4/8) and macrophages, but individual CD20+ cells could still be identified within the parenchyma and perivascular cuffs.

    Conclusions: This case underscores the fact that lymphocytic inflammation in plaques, including B-cells, is not completely abrogated following treatment with Rituximab, even with undetectable peripheral CD20+ B cell counts.
     
    ErdemX, Mij, Manganus and 6 others like this.
  2. Jesse2233

    Jesse2233 Senior Member

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    Does this have implications for the RTX non responders?
     
  3. Jonathan Edwards

    Jonathan Edwards Senior Member

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    I think not. B cells rarely survive in diseased tissue unless there is a substantial aggregate of mononuclear cells present. That means significant focal inflammation in brain of the sort that leads to the destructive lesions of MS. Also this is a very severe case with large aggregates. ME/CFS does not show this sort of cellular aggregate in brain or oligoclonal antibody production in brain. So it seems unlikely that B cells in brain are important in ME/CFS.
     
    ErdemX, Marky90, MEMum and 5 others like this.
  4. halcyon

    halcyon Senior Member

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    It's not been well reported, but this is present in some cases of ME.
     
  5. Gingergrrl

    Gingergrrl Senior Member

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    Does the fact he was JCV+ going into Rituximab play any role?
     

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