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EBioMedicine. 2017 Feb;16:41-50. doi: 10.1016/j.ebiom.2017.01.042. Epub 2017 Jan 31.

Memory B Cells are Major Targets for Effective Immunotherapy in Relapsing Multiple Sclerosis.

Author information

1
Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, United Kingdom.
2
Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, United Kingdom. Electronic address: k.schmierer@qmul.ac.uk.

Abstract

Although multiple sclerosis (MS) is considered to be a CD4, Th17-mediated autoimmune disease, supportive evidence is perhaps circumstantial, often based on animal studies, and is questioned by the perceived failure of CD4-depleting antibodies to control relapsing MS. Therefore, it was interestingly to find that current MS-treatments, believed to act via T cell inhibition, including: beta-interferons, glatiramer acetate, cytostatic agents, dimethyl fumarate, fingolimod, cladribine, daclizumab, rituximab/ocrelizumab physically, or functionally in the case of natalizumab, also depleted CD19+, CD27+ memory B cells. This depletion was substantial and long-term following CD52 and CD20-depletion, and both also induced long-term inhibition of MS with few treatment cycles, indicating induction-therapy activity. Importantly, memory B cells were augmented by B cell activating factor (atacicept) and tumor necrosis factor (infliximab) blockade that are known to worsen MS. This creates a unifying concept centered on memory B cells that is consistent with therapeutic, histopathological and etiological aspects of MS.

KEYWORDS:

Autoimmunity; Disease modifying treatment; Immunotherapy; Memory B cell; Multiple sclerosis

PMID:
28161400
PMCID:
PMC5474520
DOI:
10.1016/j.ebiom.2017.01.042
[Indexed for MEDLINE]
Free PMC Article

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