Tuesday, 22 December 2015

NSS-Depletion of B cells can make you more liable for infection

Gilli F, Li L, Campbell SJ, Anthony DC, Pachner AR. The effect of B-cell depletion in the Theiler's model of multiple sclerosis. J Neurol Sci. 2015;359(1-2):40-47.

B cell depletion (BCD) is being considered as a treatment for multiple sclerosis (MS), but there are many uncertainties surrounding the use of this therapy, such as its potential effect in individuals with concurrent viral infections. We sought to discover what effect BCD, induced by an anti-CD20 monoclonal antibody, would have on Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Mice were injected with the anti-CD20 monoclonal antibody 5D2, 14days before or 14days after infection with TMEV. Efficacy of depletion of B cells was assessed by flow cytometry of CD19+ cells. Mouse disability was measured by Rotarod, viral load was measured by real time PCR for TMEV RNA. Binding and neutralizing antibody levels were determined in sera and CSF by ELISA, and in CNS by real time PCR for IgG RNA. Inflammation, microglial activation, axonal damage and demyelination were assessed using immunohistochemistry. 5D2-induced BCD was confirmed by demonstration of nearly absent CD19+ cells in the blood and lymphoid tissue. Systemic and CNS antibody responses were suppressed during 5D2 treatment. Higher viral loads were detected in 5D2-treated mice than in controls, and the viral levels correlated negatively with IgG production in the brain. Overall, 5D2 caused worsening of the early encephalitis and faster progression of disability, as well as exacerbation of the pathology of TMEV-IDD at the end stage of the disease. These data indicate that BCD in humans might worsen CNS viral infections and might not improve disability accrual in MS.


As ocrelizumab starts to become useful, animal modelllers I suspect and going to jump through hoops to show that they are B cell mediated. In EAE there is already data to say it can inhibit disease or does it really....in fact the best data is in CD20 transgenic mice treated with rixuximab and EAE is eliminated...only problem is this treatement is associated with an CD80% reduction in T cells...so surprsise, surprise it inhibits EAE. 

But what about viral models of MS....So deplete B cells and give mice damaging virus and surprise surprise disease gets worse, because B cells are needed to get rid of the viruses, in addition to CD8+ T cells, which was know about for a while. In fact one of the major side effects of anti-CD20 depletion in humans are viral infections go figure. 

Someone from RSPCA recently said that we should publish all animal-related MS work to save beasties being used, wonder what 5 min of reading would do first?

3 comments:

  1. But Fingolimod, Alemtuzumab, Tysabre and Tecfidera also do this, each in its "degree" of vulnerability to allow infections ...

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  2. So is the takeaway basically: If someone where to attempt treatment with Ocrelizumab, it might be prudent to first check for the presence of common viral infections of the CNS before proceeding?

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  3. MD,

    Have not heard NSS in years but I suspect this means No Sh1t Sherlock or is it a National Something Society

    ReplyDelete

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