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Journal Article
Review
Relevance of Pathogenetic Mechanisms to Clinical Effectiveness of B-Cell-Depleting Monoclonal Antibodies in Multiple Sclerosis.
Journal of Clinical Medicine 2022 July 24
Evidence of the effectiveness of B-cell-depleting monoclonal antibodies (mAbs) in multiple sclerosis (MS) prompted a partial revisitation of the pathogenetic paradigm of the disease, which was, so far, considered a T-cell-mediated autoimmune disorder. Mechanisms underlying the efficacy of B-cell-depleting mAbs in MS are still unknown. However, they likely involve the impairment of pleiotropic B-cell functions different from antibody secretion, such as their role as antigen-presenting cells during both the primary immune response in the periphery and the secondary response within the central nervous system (CNS). A potential impact of B-cell-depleting mAbs on inflammation compartmentalised within the CNS was also suggested, but little is known about the mechanism underlying this latter phenomenon as no definite evidence was provided so far on the ability of mAbs to cross the blood-brain barrier and reliable biomarkers of compartmentalised inflammation are lacking. The present paper briefly summarises the immunopathogenesis of MS with a focus on onset of autoimmunity and compartmentalisation of the immune response; mechanisms mediating B-cell depletion and underlying the effectiveness of B-cell-depleting mAbs are also discussed.
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