Review of pathogenic mechanisms in MS

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frodo
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Review of pathogenic mechanisms in MS

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Relevance of Pathogenetic Mechanisms to Clinical Effectiveness of B-Cell-Depleting Monoclonal Antibodies in Multiple Sclerosis

https://www.mdpi.com/2077-0383/11/15/4288/htm

Abstract

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.

Conclusions

The mechanisms underlying the suppression of inflammatory activity induced by B-cell depletion are only partially known and possibly involve pleiotropic roles of B cells, being the impairment of the antigen-presenting function the most plausible candidate. However, it is not clear yet if B-cell-depleting mAbs can act only in the peripheral compartment or if they also affect compartmentalised inflammation, as may be suggested by evidence of efficacy in progressive disease.

Further knowledge of the impact of anti-CD20 mAbs on compartmentalised inflammation and of mechanisms underlying their potential effectiveness is needed to promote a tailored therapeutic approach, possibly offering additional treatment opportunities in progressive MS, an area where a remarkable unmet clinical need persists
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