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Role of complement and potential of complement inhibitors in myasthenia gravis and neuromyelitis optica spectrum disorders: a brief review

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A Correction to this article was published on 15 November 2021

A Correction to this article was published on 17 October 2019

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Abstract

The complement system is a powerful member of the innate immune system. It is highly adept at protecting against pathogens, but exists in a delicate balance between its protective functions and overactivity, which can result in autoimmune disease. A cascade of complement proteins that requires sequential activation, and numerous complement regulators, exists to regulate a proportionate response to pathogens. In spite of these mechanisms there is significant evidence for involvement of the complement system in driving the pathogenesis of variety of diseases including neuromyelitis optica spectrum disorders (NMOSD) and myasthenia gravis (MG). As an amplification cascade, there are an abundance of molecular targets that could be utilized for therapeutic intervention. Clinical trials assessing complement pathway inhibition in both these conditions have recently been completed and include the first randomized placebo-controlled trial in NMOSD showing positive results. This review aims to review and update the reader on the complement system and the evolution of complement-based therapeutics in these two disorders.

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Authors and Affiliations

  1. Ipsen Biopharm Ltd, 9 Ash Rd N, Wrexham, LL13 9UF, UK

    Jayne L. Chamberlain

  2. Department of Neurology, The Walton Centre, Lower Lane, Liverpool, L9 7LJ, UK

    Saif Huda, Daniel H. Whittam & Anu Jacob

  3. Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA

    Marcelo Matiello

  4. School of Medicine, Henry Wellcome Building for Biomedical Research, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN, UK

    B. Paul Morgan

  5. University of Liverpool, Liverpool, UK

    Anu Jacob

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AJ: Principal Investigator for the ECU301 and ECU302 trials on Eculizumab in neuromyelitis optica in the UK. AJ has also received research grants from Alexion Pharmaceuticals, Biogen Idec and speaker fees from Biogeb, Chugai, Sanofi-Genzyme and Terumo-BCT. MM: Adboard consulting for Alexion Pharmaceuticals. JC, SH, DH and BPM have no conflicts of interest.

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Chamberlain, J.L., Huda, S., Whittam, D.H. et al. Role of complement and potential of complement inhibitors in myasthenia gravis and neuromyelitis optica spectrum disorders: a brief review. J Neurol 268, 1643–1664 (2021). https://doi.org/10.1007/s00415-019-09498-4

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