Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8438588 | EBioMedicine | 2017 | 10 Pages |
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 CD19Â +, CD27Â + 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
TNFHSCTDMDmAbEAEexperimental autoimmune encephalomyelitisAPRILMRIEBVAIDSimmunotherapyinterleukinBAFFMagnetic resonance imagingautoimmunityDisease modifying treatmentCNSMemory B cellacquired immunodeficiency syndromecentral nervous systemB cell activating factortumor necrosis factorB lymphocyte stimulatorMultiple sclerosisEpstein barr virusHIVhuman immunodeficiency virusMonoclonal antibodiesa proliferation-inducing ligand
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Cancer Research
Authors
David Baker, Monica Marta, Gareth Pryce, Gavin Giovannoni, Klaus Schmierer,