Eculizumab improved weakness and taste disorder in thymoma-associated generalized myasthenia gravis with anti-striational antibodies: A case report

Amano, Eiichiro; Otsu, Shinichi; Suzuki, Shigeaki; Machida, Akira

doi:10.1016/j.ensci.2019.01.006

Cited by 10 publications

(15 citation statements)

References 9 publications

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Section: Complement Inhibition In Mg Therapeuticsmentioning

confidence: 99%

“…To this purpose, biomarker validation for clinical usage on a large scale will be a critical step, for which well-designed retrospective or prospective clinical trials will be needed. Retrospective analyses could be performed on samples obtained from the clinical trials already completed, 58 , 59 , 66 for which the outcome data are available. Collection of biological samples is an essential condition for allowing retrospective biological analyses; thus, it should be considered a key step during clinical trials.…”

Section: Biomarkers For Tailoring and Monitoring Complement-targeted mentioning

confidence: 99%

“…However, recent evidences of case reports demonstrate that eculizumab represents a valid therapeutic approach also for thymoma-associated MG, which strongly associates with treatment-refractory disease. 65,66 Ravulizumab Ravulizumab (Ultomiris) is another recombinant humanized monoclonal antibody developed by Alexion Pharmaceuticals that binds the complement protein C5 with high affinity. Ravulizumab was primarily tested and then approved for PNH in the USA, following positive results of two phase III clinical trials, on December 2018.…”

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confidence: 99%

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<p>Complement Inhibition for the Treatment of Myasthenia Gravis</p>

Mantegazza

Vanoli

Frangiamore

et al. 2020

ITT

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Generalized myasthenia gravis (gMG) is a rare autoimmune disorder affecting the neuromuscular junction (NMJ). Approximately 80–90% of patients display antibodies directed against the nicotinic acetylcholine receptor (AChR). A major drive of AChR antibody-positive MG pathology is represented by complement activation. The role of the complement cascade has been largely demonstrated in patients and in MG animal models. Complement activation at the NMJ leads to focal lysis of the post-synaptic membrane, disruption of the characteristic folds, and reduction of AChR. Given that the complement system works as an activation cascade, there are many potential targets that can be considered for therapeutic intervention. Preclinical studies have confirmed the efficacy of complement inhibition in ameliorating MG symptoms. Eculizumab, an antibody directed towards C5, has recently been approved for the treatment of AChR antibody-positive gMG. Other complement inhibitors, targeting C5 as well, are currently under phase III study. Complement inhibitors, however, may present prohibitive costs. Therefore, the identification of a subset of patients more or less prone to respond to such therapies would be beneficial. For such purpose, there is a critical need to identify possible biomarkers predictive of therapeutic response, a field not yet sufficiently explored in MG. This review aims to give an overview of the complement cascade involvement in MG, the evolution of complement-inhibiting therapies and possible biomarkers useful to tailor and monitor complement-directed therapies.

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Section: Complement Inhibition In Mg Therapeuticsmentioning

confidence: 99%

Section: Biomarkers For Tailoring and Monitoring Complement-targeted mentioning

confidence: 99%

mentioning

confidence: 99%

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<p>Complement Inhibition for the Treatment of Myasthenia Gravis</p>

Mantegazza

Vanoli

Frangiamore

et al. 2020

ITT

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“…19 Eculizumab is a monoclonal antibody that specifically binds with high affinity to human terminal complement protein C5, and is expected to be effective in refractory MG patients with StrAbs. 20 In addition, the presence of anti-titin antibodies in patients with MG is correlated with the myopathic features in electromyography. 21 In contrast, anti-RyR antibodies cause allosteric inhibition of RyR function in vitro, inhibiting Ca 2+ release from the sarcoplasmic reticulum.…”

Section: Immunolog Ic Al Profile Smentioning

confidence: 99%

“…With regard to the pathogenesis of autoantibodies, complement activation by anti‐titin antibodies was also shown 19 . Eculizumab is a monoclonal antibody that specifically binds with high affinity to human terminal complement protein C5, and is expected to be effective in refractory MG patients with StrAbs 20 . In addition, the presence of anti‐titin antibodies in patients with MG is correlated with the myopathic features in electromyography 21 .…”

Section: Immunological Profilesmentioning

confidence: 99%

Anti‐striational antibodies: Expanding their clinical significance

Suzuki

Nagane

Uzawa

et al. 2020

Clinical & Exp Neuroim

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Myasthenia gravis (MG) is an organ-specific autoimmune disorder generally mediated by anti-acetylcholine receptor (AChR) or, less frequently, by anti-muscle-specific tyrosine antibodies at the neuromuscular junction. 1 In the 1970s, before the discovery of anti-AChR antibodies, anti-striational antibodies (StrAbs) were known as serum immunoglobulins that react with cross-striations of skeletal muscle in MG patients. Indirect immunofluorescence of animal skeletal muscle tissue was the original method for detecting StrAbs. 2 StrAbs had been expected to be useful as biomarkers of MG; however, immunoreactivity on indirect immunofluorescence was also observed in other disorders and in normal controls. Because of the low specificity of StrAbs as biomarkers, the diagnostic utility of StrAbs had been regarded to be limited. In the 1990s, several molecules on skeletal and heart muscle proteins were identified as autoantigens of StrAbs. In particular, the

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Eculizumab treatment for myasthenia gravis subgroups: 2021 update

2022

Journal of Neuroimmunology

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Eculizumab improved weakness and taste disorder in thymoma-associated generalized myasthenia gravis with anti-striational antibodies: A case report

Cited by 10 publications

References 9 publications

<p>Complement Inhibition for the Treatment of Myasthenia Gravis</p>

<p>Complement Inhibition for the Treatment of Myasthenia Gravis</p>

Anti‐striational antibodies: Expanding their clinical significance

Eculizumab treatment for myasthenia gravis subgroups: 2021 update

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