However, whilst ProfG has been munching on his chapeau, I’ve been doing some reading and am not ready to let the T cell boys and girls off the hook. More B cell magic….
BTK plays a crucial role in B cell maturation. Mutations in the BTK gene are implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton’s agammaglobulinemia); sometimes abbreviated to XLA.
They do not make antibody because the cells making antibody have gone, so a functional depletion or an absolute depletion.
Patients with XLA have normal pre-B cell populations in their bone marrow but these cells fail to mature and enter the circulation.
BTK expression was up-regulated upon B cell receptor stimulation in vitro and was significantly expressed in CD27+ memory B cells.
There is a depletion of memory B cells so the idea on the pathogenesis of MS is still alive and kicking…so split you hat out
Agematsu K, Futatani T, Hokibara S, Kobayashi N, Takamoto M, Tsukada S, Suzuki H, Koyasu S, Miyawaki T, Sugane K, Komiyama A, Ochs HD. Absence of memory B cells in patients with common variable immunodeficiency. Clin Immunol. 2002;103(1):34-42.
Know what happens with the therapeutic.
Has profG have been sold a dummy?
Maybe he is under the impression that there is no B cell depletion and it is functionally inhibiting the cells, but is it true?
Not in the mouse, its not.
So all you pharma people with BTK inhibitors…Please Please Please remember that B cells are not a single amorphous CD19 B cell population do the subsets
We have been looking the “you know what drug” at 12 months after drug there is no CD19 B cell depletion, but look at the memory B cell populations and they are still wiped out.
So what happenes to the Merck drug. It is an irrevesible drug, so once bound to the BTK it is inhibited.
Now mouse B cells aren’t the same as human B cells but lets look at an abstract on
Philipp Haselmayer et al. Pharmacodynamic Modeling of BTK Occupancy Versus Efficacy in Ra and SLE Models Using the Novel Specific BTK Inhibitor Evobrutinib.
Not wishing to be rude but could someone please proofread this?