#MSresearch B cells role in EAE more wishful thinking
This is a repost but you get access to paper now
Eseberuo Sefia, Gareth Pryce, Ute-Christiane Meier, Gavin Giovannoni, David Baker Depletion of CD20 B cells fails to inhibit relapsing mouse experimental autoimmune encephalomyelitis. Mult scleros is and related disorders DOI: http://dx.doi.org/10.1016/j.msard.2017.03.013
Background. Multiple sclerosis (MS) is often considered to be a CD4, T cell-mediated disease. This is largely based on the capacity of CD4 T cells to induce relapsing experimental autoimmune encephalomyelitis (EAE) in rodents. However, CD4-depletion using a monoclonal antibody was considered unsuccessful and relapsing MS responds well to B cell depletion via CD20 B cell depleting antibodies. The influence of CD20 B cell depletion in relapsing EAE was assessed.
Methods. Relapsing EAE was induced in Biozzi ABH mice. These were treated with CD20-specific (18B12) antibody and the influence on CD45RA-B220 B cell depletion and clinical course was analysed.
Results. Relapsing EAE in Biozzi ABH failed to respond to the marked B cell depletion induced with a CD20-specific antibody. In contrast to CD20 and CD8-specific antibodies, CD4 T cell depletion inhibited EAE.
Conclusion. Spinal cord antigen-induced disease in ABH mice is CD4 T cell-dependent. The lack of influence of CD20 B cell depletion in relapsing EAE, coupled with the relatively marginal and inconsistent results obtained in other mouse studies, suggests that rodents may have limited value in understanding the mechanism occurring following CD20 B cell depletion in humans
UNTIL 25 MAY 2017 YOU CAN CLICK ON THE LINK BELOW FOR FREE ACCESS
They went through the mechanisms of how CD20 depleting antibodies work.
1. They dismissed a roll for antibodies as CD20 does not quickly deplete antibodies, because it does not deplete plasma cells
2. They didn't even think of the viral reservoir idea.
3. They said that they worked on antigen presentation,
because that is what the animals studied showed.
I said "If the animal results are based on dogey-ground,
Where does it leave the hypothesis?"
So hot off the press...Here we go.
What did anti-CD20 do in the beasties?
Major depletion of B cells, but that is where the good data ends.
What does it do Relapsing EAE?
In our hands........Nada...Nyet...Nothing!
However, deplete CD4 T cells and disease is gone!
So how do you report this?
I thought we could put it in the context of other studies
So what have other people found?
It made us look at the data
So rather than write about it, where it would go in one ear and out the next.
I thought it was easier to pay for the copyright fees to get permission to reproduce the figures in the paper, so you can all see for yourself.
I showed DrK the figure below, before he knew what the content was and he said "What ever it is, it doesn't look very good"
What's your take?
(A) Shows depending on when start treatment to induce CD20 B
cell depletion it can either:
- Do Nothing
- Inhibit Disease
let’s face it. It’s only a partial inhibit, not a wipe out like fingolimod or
CD52 antibody could do.
(C) Shows so called B cell-dependent EAE where anti-CD20 works,
there is a non-B dependent EAE induced with peptide that doesn't work.
However, I thought “Hang on. That's the same EAE used in A &
C were the antibody is working, so is it B cell independent?
In addition if you treat before disease induction it's worse in (A),
but better in (B) and (C). So not consistent.
But really as DrK says. The effect in (A) & (C) are rather
So the effect in (B) saves the day...yeah it flat lines disease.
But look at the graph at the bottom of (B) on the left. It says
B cells were depleted out or sight. But in (B) on right CD4 T cells were also
depleted out of sight, so if you deplete T cells with anti-CD20.....it works in
animals. So the answer is that the results says that rodent EAE is a T cell
I have no issues with that, but as we have been saying it looks
like T cell depletion isn’t that effective in MS.
So no major T cell Depletion with the anti-CD20 antibody we used
and there was no effect on EAE.
So if it is antigen-presentation?
Shouldn't the B cell depletion do better if it was?
Are you still an antigen-presenting B cell fan?
But, is this how anti-CD20 works in MS?
Maybe Mice can't give us the answer.
Maybe we should also say marmoset EAE failed to predict the effect of BAFF/APRIL
Maybe the answer can only be found by studying humans
CoI: This is work from TeamG