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

Autor: Klaus Schmierer, Gareth Pryce, David Baker, Monica Marta, Gavin Giovannoni
Rok vydání: 2017
Předmět:
0301 basic medicine
lcsh:Medicine
Autoimmunity
Review
Atacicept
0302 clinical medicine
Natalizumab
Daclizumab
Molecular Targeted Therapy
Memory B cell
EAE
experimental autoimmune encephalomyelitis
B-Lymphocytes
TNF
tumor necrosis factor
lcsh:R5-920
General Medicine
Fingolimod
HIV
human immunodeficiency virus
medicine.anatomical_structure
BAFF
B cell activating factor
Cytokines
Rituximab
Immunotherapy
Inflammation Mediators
Gd +
gadolinium-enhancing
lcsh:Medicine (General)
medicine.drug
APRIL
a proliferation-inducing ligand
T cell
Plasma Cells
CNS
central nervous system
General Biochemistry
Genetics and Molecular Biology
MS
multiple sclerosis
Multiple sclerosis
03 medical and health sciences
Multiple Sclerosis
Relapsing-Remitting
EBV
Epstein Barr virus
Disease modifying treatment
medicine
Humans
business.industry
(BLyS)
B lymphocyte stimulator
lcsh:R
Models
Immunological
mAb
monoclonal antibodies
medicine.disease
AIDS
acquired immunodeficiency syndrome
IL
interleukin
DMD
disease modifying drug
030104 developmental biology
Immunology
business
Immunologic Memory
HSCT
hematopoietic stem cell therapy
MRI
magnetic resonance imaging
030217 neurology & neurosurgery
Zdroj: EBioMedicine, Vol 16, Iss C, Pp 41-50 (2017)
EBioMedicine
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2017.01.042
Popis: 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.
Highlights • Memory B cells activity is consistent with the etiology, pathology and therapy of MS, thought to be T cell-mediated. • Deletion of memory B cells occurs with all effective MS treatments and is more marked with high-efficacy treatments. • Drugs that worsen MS, can also increase memory B cell production.
Databáze: OpenAIRE
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