End of Year Revision

As the year draws to a close, it has been a productive year for papers and ideas. 

I predict that during 2018, we will get even more clarity on the story.

But do you believe the academic minnow or the whale?

As we have said many times before, people do not all agree on the driving force of MS.

Most people are still in the T cell camp or midway into the T cell camp. Even those in the B cell camp are not convinced and so do not provide any clarity into what is going on. 

Is it Chewbacca Science, like the chewbacca defence...you throw a load of facts in the air and it simply confuses every one, so every one agrees with you but non-one knows what's really going on. 

You are never wrong because you suggest every possibility. Everyone is happy.

However, it allows you to lack focus and so waste time by not doing the important things.

 Chewbacca Science-Lovely and Cuddly

Greenfield AL, Hauser SL.B Cell Therapy for Multiple Sclerosis: Entering an Era. Ann Neurol. 2017. doi: 10.1002/ana.25119.

Monoclonal antibodies that target CD20 expressing B cells represent an important new treatment option for patients with multiple sclerosis (MS). B cell depleting therapy is highly effective against relapsing forms of the disease and is also the first treatment approach proven to protect against disability worsening in primary progressive MS. Moreover, evolving clinical experience with B cell therapy, combined with a more sophisticated understanding of humoral immunity in preclinical models and in patients with MS, have led to major progress in deciphering the immune pathogenesis of MS. Here, we review the nuanced roles of B cells in MS autoimmunity, the clinical data supporting the use of ocrelizumab and other anti-CD20 therapies in the treatment of MS, as well as safety and practical considerations for prescribing. Lastly, we summarize remaining unanswered questions regarding the proper role of anti-CD20 therapy in MS, its limitations, and the future landscape of B cell-based approaches to treatment. 

In my opinion, this paper seems to be little more than an advert for ocrelizumab, particularly as it states the manufactures provide "writing assistance for CD20-related presentations"

Anyway, it says:

"Although most disease-modifying therapies for MS have traditionally been conceptualized as functioning via T cell-based mechanisms, a growing body of data indicates that all have demonstrable effects on B cells as well".

"Common themes include 
  • Promoting naive rather than memory or plasmablast (alemtuzumab); 
  • Shifting B cell cytokines towards an anti-inflammatory tone (beta interferon, glatiramer acetate, fingolimod);
  • Increasing B-regs (beta interferon, glateriamer acetate, fingolimod and dimethyl fumarate); 
  • Decreasing class II MHC and constimulatory molecules on B cells required for antigen presentation (beta interferon and dimethyl fumarate); 
  • Sequestering B cells in lymphoid organs (fingolimod); 
  • Blocking VLA-4 mediated B cell trafficking to the CNS (natalizumab); or
  • Direct cytolysis of B cells (alemtuzumab, teriflunomide, mitoxantrone)" 
As for ocrelizumab
  • Potentially pathogenic memory B cells remain at reduced levels
  • Fewer GM-CSF producing B cells and higher levels of IL-10
  • Fewer pro-inflammatory Th1 & Th17 cells
  • Large number of CD25+FOXP3 regulatory T cells
So as the year draws to a close, 

I ask you to remember what you have learnt this year and ask you to consider this ....

Do you want to believe the Jumble of Conflicting and Inconsistent Ideas? as all the above are possible. It means the MS treatment landscape is difficult to comprehend and navigate or

Is it simpler that MS treatments all physically or functionally deplete memory B cells (maybe to stop them becoming plasmablasts) to prevent them entering the CNS.

This gives a unifying idea on aetiology, pathology and response to treatment?

It makes treatment choices easier.

Baker D, Marta M, Pryce G, Giovannoni G, Schmierer K. Memory B Cells are Major Targets for Effective Immunotherapy in Relapsing Multiple Sclerosis. EBioMedicine. 2017;16:41-50.

Which fits the MS reality?

Let's put it to the test and see what happens in 2018.

I predict that more people will fall off the fence

Or maybe I'll eat humble pie.