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  • Review Article
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Myasthenia gravis — autoantibody characteristics and their implications for therapy

Nature Reviews Neurology volume 12, pages 259–268 (2016)Cite this article

Subjects

Key Points

  • The characteristic muscle weakness in myasthenia gravis (MG) is caused by antibodies directed against the neuromuscular junction

  • MG is divided into subgroups on the basis of specific antibodies, other biomarkers, and clinical characteristics, such as age of onset, presence of thymoma, and involvement of ocular muscles

  • The most common antibodies detected in MG are antibodies against acetylcholine receptors (AChRs), muscle-specific kinase (MuSK) and low-density lipoprotein receptor-related protein 4 (LRP4)

  • Additional antibodies of interest in MG are directed against agrin, titin, KV1.4, ryanodine receptors, collagen Q, and cortactin

  • Therapy should be tailored to the individual patient and guided by MG subgroup, and can include symptomatic drug therapy, immunosuppressive drug therapy, thymectomy and/or supportive therapy

  • The aim of treatment should be normal or near-normal function, which in most patients requires long-term immunosuppressive treatment with a drug combination that is individualized for the patient for optimal effectiveness

Abstract

Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies that target the neuromuscular junction, leading to muscle weakness and fatigability. Currently available treatments for the disease include symptomatic pharmacological treatment, immunomodulatory drugs, plasma exchange, thymectomy and supportive therapies. Different autoantibody patterns and clinical manifestations characterize different subgroups of the disease: early-onset MG, late-onset MG, thymoma MG, muscle-specific kinase MG, low-density lipoprotein receptor-related protein 4 MG, seronegative MG, and ocular MG. These subtypes differ in terms of clinical characteristics, disease pathogenesis, prognosis and response to therapies. Patients would, therefore, benefit from treatment that is tailored to their disease subgroup, as well as other possible disease biomarkers, such as antibodies against cytoplasmic muscle proteins. Here, we discuss the different MG subtypes, the sensitivity and specificity of the various antibodies involved in MG for distinguishing between these subtypes, and the value of antibody assays in guiding optimal therapy. An understanding of these elements should be useful in determining how to adapt existing therapies to the requirements of each patient.

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Figure 1: Neuromuscular junction in myasthenia gravis (MG).

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Article 02 May 2019

Nils Erik Gilhus, Socrates Tzartos, … Jan J. G. M. Verschuuren

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Acknowledgements

N.E.G., G.O.S. and F.R. have received funding from Torbjørg Hauge's Legacy for Neurological Research and from the Norwegian Muscle Disease Association. S.J.T., K.L. and P.Z. have received grants from the Muscular Dystrophy Association of the USA and from the Greek National Strategic Reference Framework (NeuroID ISR-3257).

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Authors and Affiliations

  1. Department of Clinical Medicine, University of Bergen, Postboks 7804, Bergen, 5020, Norway

    Nils Erik Gilhus, Geir Olve Skeie & Fredrik Romi

  2. Department of Neurology, Haukeland University Hospital, Postbox 1400, Bergen, 5021, Norway

    Nils Erik Gilhus, Geir Olve Skeie & Fredrik Romi

  3. Department of Neurobiology, Hellenic Pasteur Institute, 127 Vassilissis Sofias Avenue 115 21, Ampelokipi, Athens, Greece

    Konstantinos Lazaridis, Paraskevi Zisimopoulou & Socrates Tzartos

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All authors researched data for the Review, made substantial contributions to the discussion of the content of the article and reviewed and edited the manuscript before submission. N.E.G and S.T. wrote the article.

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Correspondence to Nils Erik Gilhus.

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Competing interests

N.E.G. has received speaker's honoraria from Octapharma, Baxter and Merck Serono. P.Z. is co-inventor in a patent related to myasthenia gravis therapy and diagnosis. S.T. is co-inventor in two patnets related to myasthenia gravis therapy and diagnosis, and is shareholder and scientific advisor of Tzartos Neurodiagnostics. Other authors declare no competing interests.

PowerPoint slides

Glossary

Antigenic modulation

Bivalent antibodies can cause crosslinking of receptors and subsequent receptor internalization.

Epitope pattern

An epitope is a localized region on an antigen capable of eliciting an immune response, and the epitope pattern refers to all epitopes involved in an immune response.

MG crisis

Severe worsening of myasthenic weakness that requires intubation or noninvasive ventilation to avoid intubation.

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Gilhus, N., Skeie, G., Romi, F. et al. Myasthenia gravis — autoantibody characteristics and their implications for therapy. Nat Rev Neurol 12, 259–268 (2016). https://doi.org/10.1038/nrneurol.2016.44

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