Acta Neuropathologica: The effect of BTK's inhibition on the progression of pathogenic B cells in inflammatory central nervous system demyelinopathy.

Over the past decade, there has been a fundamental change in perceptions of the role of B-cells in the onset and spread of multiple sclerosis.
recent evidence, a key characteristic of B cells in MS is their ability to identify antigens with B-cell receptor (BCR) specificity and to present introverted, processed antigens to reactive T cells through MHC II. the success of
anti-CD20 antibodies in MS clinical trials confirmed this concept, where the depletion of peripheral B cells quickly prevented the development of new central nervous system MS lesions.
Despite this basic achievement, the extinction of a relatively small number of highly differentiated antigen-specific B cells is associated with clinical stability, while a large number of CD20-positive B cells, including subgroups with regulatory properties that wish to remain in MS, are incidentally removed.
in addition, because MS is a chronic disease that requires long-term treatment.
over time, the continued reduction of pan-B cells and the increased risk of autosuppression of body fluids may not be a lasting strategy for decades to control disease-causing B-cell function.
new B-cell-oriented MS therapy is being pioneered, based on the limitations of anti-CD20 treatment and a deeper understanding of how B-cell subgroups trigger MS activity.
a promising approach is to inhibit Bruton tyrosine kinase (BTK), an enzyme that is directly involved in B-cell activation during bCR antigen recognition.
this paper aims to provide a mechanism for this critical clinical trial by isolating the role of evobrutinib in mouse MS models and converting the results of the observations back to the immune cells of MS patients.
method: Mice through the heart irrigation PBS added 4% polyformaldehyde, tissue paraffin encapsulation buried.
slicing (1 m) is dyed with sumuin-Ihong (HE) and Luxol-resistant blue/periodic acid shift.
use anti-biotin-biotin immunohiscitis technology to detect T-cells, B-cells, and macrophages using antibodies for CD3 (clone SP7), CD45R/B220 (clone RA3-6B2) and Mac-3 (clone M3/84).
histological slices are taken using a digital camera or VS120 slide scanner mounted on an optical microscope.
use ImageJ to calculate the percentage of demyelined white matter.
use auto-paired counting macros on HE-stained slides to evaluate overall immune cell immersion.
in a 400x magnifying glass, the inflammatory cells are quantified with an eyepiece counting grid, as cell/mm2.
at least 4 spinal cord cross-sections were taken at a time for each analysis.
Summary: The data in this paper establish and emphasize the therapeutic BTK inhibition of disease-driven B-T cell interactions in inflammatory central nervous system demyelination and does not require permanent removal of any cell type.
this is the first clinical trial of the BTK inhibitor evobrutinib in MS, and the immunotherapy effects it states may also apply to other BTK inhibitors in clinical development.
Torke, S., Pretzsch, R., H?usler, D. et al. Inhibition of Bruton's tyrosine kinase with the oedd B-cell in the rhymon CNs demyelinating disease. Acta Neuropathol (2020 !-- !--).