Thursday, 27 April 2017

AAN2017. B cells remain in the brain after rituximab treatment

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.

It is clear in arthritis that some people with arthritis relapse despite depletion of B cells in the blood and this case shows that the same is the case in MS, however it also shows us that these systemically adminsitered agents do not effectively deplete cells from the brain. 

7 comments:

  1. but he was improved significantly and only 2 years were when he was treated with a highly effective drug! I think we should 'forgot' every drug below Gilenya after diagnosed MS!

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  2. Why would this conclusion be a surprise? Rituximab/Ocrelizumab do not cross into the CNS with an intact BBB. Do the +CD20 B cells stem from an incomplete clearance by Rituximab in the periphery or from lymphoid tissue in the CNS?

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    1. It wasn't but it shows that simply removing the periperhal immune response may not remove whats in the CNS> However I really like your suggestion for an explanation. SteveS is right you can't say.

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  3. IV & IT-dosed rituximab only depleted B-cells in csf by 10% in the Revitalize trial.

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    1. That was based on CSF this shows the tissue.

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  4. Who knows long term.. looks like very aggressive MS and CD20+ cells could be detected on autopsy but who knows how many were present pre-ritux? Also, the inflammatory milieu seemed to be well established...

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  5. In this study:https://www.ncbi.nlm.nih.gov/pubmed/25745637
    They deliver Rituxan Intrathecaly and it show depletion of B cells both in the csf and Perypheral blood
    If the patient has agressive course why would´nt they use this method?

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