More evidence that B cells are driving relapse


Rebound of disease activity after fingolimod withdrawal: Immunological and gene expression profiling.Sacco R, Emming S, Gobbi C, Zecca C, Monticelli S.Mult Scler Relat Disord. 2020 Jan 3;40:101927


Discontinuation of disease-modifying therapy with fingolimod can lead to severe Multiple Sclerosis (MS) rebound activity; however, this phenomenon remains mechanistically incompletely understood (fingolimod traps B cells in lymph glands and bone marrow and you stop fingolimod and the cells enter the blood and get into the brain and a relapse occurs…rituximab gets rid of the B cells. So there’s a start), and the short-term impact of a therapy switch on inflammatory gene expression in T lymphocytes is unknown (You could say who cares you are not looking at the right cell type, so another good example how T cell blinkers abound). We present the clinico-radiological and immunological description of a case of rebound activity after fingolimod discontinuation and switching to rituximab treatment in a relapsing-remitting MS patient (Why would a B cell depleting strategy be so successful if the issue were T cells…I guess you will say it is the 1% of CD4 T cells affected that are the key). After severe rebound (A plan should be inplace when fingolomod or natalizumab is stopped and people should switch , a reduction in the expression of inflammatory cbefore rebound occurs) cytokines and transcription factors was rapidly observed after administration of methylprednisolone and rituximab. Rituximab led to an effective suppression of inflammatory activity, and at least in this specific case it represented a valid switching approach after fingolimod discontinuation (There are anumber of other studies saying the same thing).

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  • And most neurologists still think that tysabri is only a t-cell modulator/blocker.

    Have you seen any recent post-mortem papers on deceased ling time users of Tysabri?

    • No sure what “ling” time is. I suspect predictive text has done you in. Not sure about post-mortem studies, we never did get the remyelination rich post-mortem study.

  • Could Tysabri/fingolimod post-mortem brains reveal the original insult that is central to the hypothesis that immune involvement is secondary in MS process? Or…IF the relapses upon Ty/fing discontinuation are in response to an unidentified infection allowed to fester while immune cells are sequestered, would infectious agent be more easily found in same p-m brains?? Anyone looking at this?

    • Good question ProfG would agree with you that tysabri/fingolimod can tell us alot, especially the rebound the problem is we should not get rebound and so we have missed the boat as we know we have to retreat with something else and not that many people on these treatments come to post mortem (OK except PML cases)

  • RA- thanks!

    Research powers that be – is the program to harvest post-mortem tysabri/fingolimod brains adequate? Surely (sadly) folks on those meds die from accidental causes and crime just as much as the next guy. I know in my American experience, no one has ever asked me for custody of my post-mortem MS brain. Perhaps researchers/governments need to be more aggressive in gathering data (no, I’m not suggesting you become white coated serial killers…though that would make a great thriller novel. Just make sure you get our brains when we don’t need them anymore). Seems like a profG type of effort to promote such a cause. “Time is brain. Btw, can we have yours??”

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