B cell targeted therapies in inflammatory autoimmune disease of the central nervous system

Moritz J Furman; Sven G Meuth; Philipp Albrecht; Michael Dietrich; Heike Blum; Jan Mares; Ron Milo; Hans-Peter Hartung

doi:10.3389/fimmu.2023.1129906

B cell targeted therapies in inflammatory autoimmune disease of the central nervous system

Front Immunol. 2023 Mar 9:14:1129906. doi: 10.3389/fimmu.2023.1129906. eCollection 2023.

Authors

Moritz J Furman¹, Sven G Meuth¹, Philipp Albrecht^{1

2}, Michael Dietrich¹, Heike Blum¹, Jan Mares³, Ron Milo⁴, Hans-Peter Hartung^{1

3

5}

Affiliations

¹ Department of Neurology, Heinrich-Heine University Düsseldorf, Medical Faculty, Düsseldorf, Germany.
² Department of Neurology, Maria Hilf Clinic, Moenchengladbach, Germany.
³ Department of Neurology, Palacky University in Olomouc, Olomouc, Czechia.
⁴ Department of Neurology, Barzilai Medical Center, Ashkelon, Israel.
⁵ Brain and Mind Center, Medical Faculty, The University of Sydney, Sydney, NSW, Australia.

Abstract

Cumulative evidence along several lines indicates that B cells play an important role in the pathological course of multiple sclerosis (MS), neuromyelitisoptica spectrum disorders (NMOSD) and related CNS diseases. This has prompted extensive research in exploring the utility of targeting B cells to contain disease activity in these disorders. In this review, we first recapitulate the development of B cells from their origin in the bone marrow to their migration to the periphery, including the expression of therapy-relevant surface immunoglobulin isotypes. Not only the ability of B cells to produce cytokines and immunoglobulins seems to be essential in driving neuroinflammation, but also their regulatory functions strongly impact pathobiology. We then critically assess studies of B cell depleting therapies, including CD20 and CD19 targeting monoclonal antibodies, as well as the new class of B cell modulating substances, Bruton´s tyrosinekinase (BTK) inhibitors, in MS, NMOSD and MOGAD.

Keywords: B cell depletion; autoimmune disease of the central nervous system; multiple sclerosis (MS); myelin oligodendrocyte glycoprotein associated autoimmune disease (MOGAD); neuromyelitisoptica spectrum disorders (NMOSD).

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Autoantibodies
Autoimmune Diseases* / drug therapy
B-Lymphocytes
Central Nervous System
Humans
Multiple Sclerosis* / drug therapy

Substances

Autoantibodies

Grants and funding

SM: research is funded by the German Ministry for Education and Research BMBF, Deutsche Forschungsgemeinschaft DFG, Else Kröner Fresenius Foundation, German Academic Exchange Service, Hertie Foundation, Interdisciplinary Center for Clinical Studies IZKF Muenster, German Foundation Neurology, and by Almirall. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.