Article ; Online: Therapies for multiple sclerosis targeting B cells.
2019 Volume 60, Issue 2, Page(s) 87–98
Abstract: Increasing evidence suggests that B cells contribute both to the regulation of normal autoimmunity and to the pathogenesis of immune mediated diseases, including multiple sclerosis (MS). B cells in MS are skewed toward a pro-inflammatory profile, and ... ...
| Abstract | Increasing evidence suggests that B cells contribute both to the regulation of normal autoimmunity and to the pathogenesis of immune mediated diseases, including multiple sclerosis (MS). B cells in MS are skewed toward a pro-inflammatory profile, and contribute to MS pathogenesis by antibody production, antigen presentation, T cells stimulation and activation, driving autoproliferation of brain-homing autoreactive CD4+ T cells, production of pro-inflammatory cytokines, and formation of ectopic meningeal germinal centers that drive cortical pathology and contribute to neurological disability. The recent interest in the key role of B cells in MS has been evoked by the profound anti-inflammatory effects of rituximab, a chimeric monoclonal antibody (mAb) targeting the B cell surface marker CD20, observed in relapsing-remitting MS. This has been reaffirmed by clinical trials with less immunogenic and more potent B cell-depleting mAbs targeting CD20 - ocrelizumab, ofatumumab and ublituximab. Ocrelizumab is also the first disease-modifying drug that has shown efficacy in primary-progressive MS, and is currently approved for both indications. Another promising approach is the inhibition of Bruton's tyrosine kinase, a key enzyme that mediates B cell activation and survival, by agents such as evobrutinib. On the other hand, targeting B cell cytokines with the fusion protein atacicept increased MS activity, highlighting the complex and not fully understood role of B cells and humoral immunity in MS. Finally, all other approved therapies for MS, some of which have been designed to target T cells, have some effects on the frequency, phenotype, or homing of B cells, which may contribute to their therapeutic activity. |
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| MeSH term(s) | Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antigens, CD20/immunology ; B-Lymphocytes/physiology ; Cytokines/antagonists & inhibitors ; Cytokines/metabolism ; Humans ; Immunologic Factors/pharmacology ; Immunologic Factors/therapeutic use ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis/immunology ; Recombinant Fusion Proteins ; Rituximab/pharmacology ; Rituximab/therapeutic use |
| Chemical Substances | Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antigens, CD20 ; Cytokines ; Immunologic Factors ; Recombinant Fusion Proteins ; Rituximab (4F4X42SYQ6) ; ocrelizumab (A10SJL62JY) ; TACI receptor-IgG Fc fragment fusion protein (K3D9A0ICQ3) ; ofatumumab (M95KG522R0) ; ublituximab (U59UGK3IPC) |
| Language | English |
| Publishing date | 2019-04-23 |
| Publishing country | Croatia |
| Document type | Journal Article ; Review |
| ZDB-ID | 1157623-6 |
| ISSN | 1332-8166 ; 0353-9504 |
| ISSN (online) | 1332-8166 |
| ISSN | 0353-9504 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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