Nguyen AL, Gresle M, Marshall T, Butzkueven H, Field J. “Monoclonal antibodies in the treatment of MS: emergence of B-cell targeted therapies”. Br J Pharmacol. 2017 Mar 20. doi: 10.1111/bph.13780. [Epub ahead of print]
Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS, and one of the most common causes of disability in young adults. Over the last decade, new disease modifying therapies have rapidly emerged, including monoclonal antibodies (mAbs) that have provided highly targeted therapies with superior efficacy compared to platform therapies. In particular, monoclonal antibodies directed against CD20-positive B cells have shown remarkable results in recent clinical trials, and renewed interest in the mechanism of B-cell depleting therapies to ameliorate relapse activity and progression in MS. In this manuscript, we will review the mechanisms of action and clinical evidence of approved and emerging mAbs, with a focus on B-cell targeted therapies
We did the same but came to very different conclusion.
Here it is all to do with B cell regulatory function rather
than B memory function.
If you work in percentages if one goes down (Memory B cell subsets) the others (Regulatory B cells) must go up.
However in some cases because we have tried to work with absolute numbers we know that B memory cells go down
We have recently published
actually surfaced first
Maybe there are alternative explanations to the view that B cells help T cells do it all.
However, this thought does not even occur on some people’s radar
So here is a standard view
Ocrelizumab in multiple sclerosis: markers and mechanisms.
Hohlfeld R, Meinl E. Lancet Neurol. 2017;16(4):259-261.
“Overall, it seems plausible that anti-CD20 therapy partly acts by eliminating the potent antigen-presenting function of B cells, a view supported by animal experiments. Furthermore, B cells produce many pro-inflammatory and anti-inflammatory cytokines. Profound B-cell depletion might therefore lead to changes in the cytokine network, dampening pathogenic T-cell responses and thereby contributing to the beneficial effect of anti-CD20 therapy in multiple sclerosis”.
therapy is not entirely specific for B cells, as it also
depletes CD20+ T cells, which are about 5% of blood
Although I am aware that the animal studies support such a mechanism, I personally think the data from treatment of animals with anti-CD20 is weak.