ProfG was never going to post on this paper, so I am doing him a favour to get his altmetrics up.
In this study, looking at the action of daclizumab, there is no major lymphopenia. This is not surprising because it takes out activated (T & B) cells, oh and increases NK cells, it leaves most cells intact.
Neuroimmunologists, have taken hold of the MS-field and every thing has to revolve around TH17 and Tregs. However,daclizumab is one of the agents that challenges this view, because daclizumab depletes Tregs, yet MS gets better...go figure.
How does this figure in the bigger picture?
I guess if you are a T cell immunologist, you just ignore it.
So if you have a T cell view then you ask do T cell numbers correlate with infections and the answer is no.
However, T cells are only half of the lymphocyte repertoire and B cells are ignored. I must admit, I ignored them too...as a T cell-mouse. However, the B cell repertoire houses long-lived antibody forming cells and these are unlikely to be depleted, thus keeping our protection against infection.
However, B cells are important in our fight against infection and so we have missed a trick by not phenotyping the B cells properly.
Importantly we must realise that B cells are not one type (this it the educational message for all:-).
In pharma graphs, we see just the CD19+ B cells as a single entity, but CD4 & CD8 naive and memory T cells and regulatory T cells. We need to breakdown the B cell subsets, because this, I think holds the key.
Does Daclizumab deplete memory B cells in MS? Maybe this links to efficacy.
Does Daclizumab deplete plasma cells in MS? Maybe this links to infection risk.
At the last ECTRIMS last year, Biogen did a wonderful study when they did extensive immunophenotyping of people treated with dimethyl fumarate. It showed that DMF gets rid of CD8 T cells and also memory B cells and depletes T regs too.
Hope they did this for daclizumab too or if not hopefully they will do this for this daclizumab
If you are pharma planning these phenotype studies...please phenotype the Beeees.