Prof Hauser is part of the "Rumble in the Jungle" which is the "burning debate" at ECTRIMS 2017. This puts two heavy weight immunologists/neurologists against other hopefully we can stream this live from Paris.
In the Blue corner we have Prof David Hafler from Yale, USA leading the charge of "MS is a T cell disease". In the Red corner we will have Prof Stephen Hauser from San Francisco USA leading the "MS is a B cell condition". The ring master is Prof David Wraith from Birmingham, UK.
This current paper is by Prof Hauser and is a review article on B cells. I wondered, if was going to be the basis for a strategy of the approach to be used in the debate?...
Hope not, as this is zzzzzzzzzzzzzzzzzzzzzzzzzing.
The paper is a simple review on the observations around the clinical trials, which has been written loads of times before.
There is not much data supporting any idea of how the therapies are actually working, but we get the standard sitting on the fence
It's an anti-T cell agent killing a miniscule population of T cells....really:-(
It then states that following B-cell therapy, "repopulating B cells consist of larger
numbers of naïve B cells and fewer antigen-educated memory
B cells and plasmablasts, possibly explaining the
continuing suppression of MS disease activity noted even after
B-cell reconstitution has occurred".
So not a lot to tell you what is going on.
Clearly our view that memory B cells are important targets has not yet gained traction.
Maybe people can't be bothered to read it......What you haven't read it yet. It's here and free.
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
So maybe it sounds like we need to shout a bit louder, so that people start to try and disprove the idea...However, so far this year it was not been difficult to build on the idea.
However, when I was presenting the data a couple of weeks ago, someone asked how does it fit into the idea that oligodendrocytes are the major target in MS.
I waffled a rubbish answer and good point I thought.
If CD4 T cells are the cause of problem one also has to struggle to answer the question too. Why? Because oligodendrocytes do not express MHC class II (a restriction element for CD4 T cells. See the education posts) in vivo and so are not going to be targeted by CD4 T cells directly so its effect would have to be indirect.
Whilst those bothered that CD4 TH17 cells are the problem can ponder this question, it is evident that B cells make factors that can kill oligodendrocytes and nerves.
Lisak RP, Nedelkoska L, Benjamins JA, Schalk D, Bealmear B, Touil H, Li R, Muirhead G, Bar-Or A. B cells from patients with multiple sclerosis induce cell death via apoptosis in neurons in vitro.J Neuroimmunol. 2017 Aug 15;309:88-99.
B cells mediate multiple sclerosis (MS) pathogenesis by mechanisms unrelated to immunoglobulin (Ig). We reported that supernatants from cultured B cells from blood of relapsing remitting MS (RRMS) patients, but not normal controls (NC), were cytotoxic to rat oligodendrocytes (OL). We now show that RRMS blood B cells, not stimulated in vitro, secrete factor/s toxic to rat and human neurons. Cytotoxicity is independent of Ig and multiple cytokines, not complement-mediated, and involves apoptosis. The factor/s have an apparent mw of >300kDa. B cells (twice the size of an IgG antibody molecule and much bigger than typical cytokines) could contribute to damage within the central nervous system by secreting molecules toxic to OL and neurons.