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B cells as therapeutic targets in autoimmune neurological disorders

Nature Clinical Practice Neurology volume 4, pages 557567 (2008) | Download Citation

Subjects

Abstract

B cells have a fundamental role in the pathogenesis of various autoimmune neurological disorders, not only as precursors of antibody-producing cells, but also as important regulators of the T-cell activation process through their participation in antigen presentation, cytokine production, and formation of ectopic germinal centers in the intermeningeal spaces. Two B-cell trophic factors—BAFF (B-cell-activating factor) and APRIL (a proliferation-inducing ligand)—and their receptors are strongly upregulated in many immunological disorders of the CNS and PNS, and these molecules contribute to clonal expansion of B cells in situ. The availability of monoclonal antibodies or fusion proteins against B-cell surface molecules and trophic factors provides a rational approach to the treatment of autoimmune neurological diseases. This article reviews the role of B cells in autoimmune neurological disorders and summarizes the experience to date with rituximab, a B-cell-depleting monoclonal antibody against CD20, for the treatment of relapsing–remitting multiple sclerosis, autoimmune neuropathies, neuromyelitis optica, paraneoplastic neurological disorders, myasthenia gravis, and inflammatory myopathies. It is expected that ongoing controlled trials will establish the efficacy and long-term safety profile of anti-B-cell agents in several autoimmune neurological disorders, as well as exploring the possibility of a safe and synergistic effect with other immunosuppressants or immunomodulators.

Key points

  • B cells have a key role in the pathogenesis of various autoimmune neurological disorders

  • A number of monoclonal antibodies or fusion proteins directed against B-cell surface molecules and trophic factors are currently in clinical trials

  • The anti-CD20 monoclonal antibody rituximab has shown promise in the treatment of disorders such as relapsing–remitting multiple sclerosis, autoimmune neuropathies, neuromyelitis optica, paraneoplastic neurological disorders, stiff-person syndrome, myasthenia gravis and inflammatory myopathies

  • Circulating B cells, but not the antibody-producing plasma cells that do not express CD20, become undetec Table 1 month after rituximab treatment, and levels remain low for at least 6 months

  • Despite B-cell depletion, patients do not seem to be prone to common infections after rituximab treatment

  • Experience in conditions such as vasculitis and rheumatoid arthritis indicates that rituximab can be used in combination with other immunosuppressants

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Acknowledgements

The author thanks Dr R Raju for performing the B-cell counts in his patients treated with rituximab.

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Affiliations

  1. MC Dalakas is Chair in Clinical Neurosciences at Imperial College London, London, UK, and Director of the Neuromuscular Disease Division at Thomas Jefferson University, Philadelphia, PA, USA.

    • Marinos C Dalakas

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Competing interests

The author declares no competing financial interests.

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DOI

https://doi.org/10.1038/ncpneuro0901

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