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REVIEW article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1502480
This article is part of the Research Topic Spotlight on Myasthenia Gravis: Pathomechanisms, diagnostic challenges and novel therapeutic targets View all articles

A clinical perspective on muscle specific kinase antibody positive myasthenia gravis

Provisionally accepted
Omar Keritam Omar Keritam 1Prof Angela Vincent Prof Angela Vincent 2Fritz Zimprich Fritz Zimprich 1Hakan Cetin Hakan Cetin 1*
  • 1 Department of Neurology, Medical University of Vienna, Vienna, Austria
  • 2 Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, England, United Kingdom

The final, formatted version of the article will be published soon.

    The discovery of autoantibodies directed against muscle-specific kinase (MuSK) in "seronegative" myasthenia gravis (MG) patients marked a milestone in MG research. In healthy muscle, MuSK regulates a phosphorylation pathway, which is essential for the development and maintenance of acetylcholine receptor (AChR) clusters at the neuromuscular junction. Autoantibodies directed against MuSK are predominantly of the IgG4 subclass, but there is increasing evidence that IgG1-3 could also contribute to the pathology underlying MuSK-MG. MuSK-IgG4 are monovalent and block the binding site for LRP4 on MuSK, thereby inhibiting the downstream phosphorylation pathway and compromising the formation of AChR clusters. Clinically, MuSK-MG is commonly associated with the predominant involvement of bulbar, facial, shoulder and neck muscles. Cholinesterase inhibitors should be avoided in MuSK-MG due to the risk of clinical impairment and cholinergic crisis. Corticosteroids and other non-steroidal immunosuppressants are less effective with the need for higher doses and prolonged treatment. Rituximab, by contrast, has been shown to be particularly effective and is now often used early in the disease course. Its use is associated with a significant improvement in the clinical outcome of MuSK-MG patients over time. This review aims to describe the pathophysiology underlying MuSK-MG and provide a comprehensive overview of the clinical features and therapeutic options.

    Keywords: Muscle-specific kinase, Myasthenia Gravis, MuSK-MG, IgG4, Neuromuscular Junction, Autoimmune disorder, review

    Received: 26 Sep 2024; Accepted: 20 Nov 2024.

    Copyright: © 2024 Keritam, Vincent, Zimprich and Cetin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Hakan Cetin, Department of Neurology, Medical University of Vienna, Vienna, Austria

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.