Presence and Pathogenic Relevance of Antibodies to Clustered Acetylcholine Receptor in Ocular and Generalized Myasthenia Gravis

Jacob, Saiju; Viegas, Stuart; Leite, Maria Isabel; Webster, Richard; Cossins, Judy; Kennett, Roger H.; Hilton‐Jones, David; Morgan, B. Paul; Vincent, Angela

doi:10.1001/archneurol.2012.437

Cited by 129 publications

(103 citation statements)

References 24 publications

(19 reference statements)

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“…In many cases, these antibodies are seen in patients with anti-AChR or antiMuSK MG, so the definitive demonstration of their pathogenicity remains to be investigated. Finally, a subset of patients with MG who are seronegative for AChR antibodies using the conventional radioimmunoprecipitation assay have been shown to have antibodies binding to clustered AChR in a cell-based assay [33][34][35]. Early reports suggest these patients tend to have less severe disease but are otherwise similar to early-onset anti-AChR-positive MG, including the presence of thymic hyperplasia [34,35].…”

Section: Mg Subtypesmentioning

confidence: 99%

Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis

2016

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Myasthenia gravis (MG) is an autoimmune disease associated with the production of autoantibodies against 1) the skeletal muscle acetylcholine receptor; 2) muscle-specific kinase, a receptor tyrosine kinase critical for the maintenance of neuromuscular synapses; 3) low-density lipoprotein receptor-related protein 4, an important molecular binding partner for muscle-specific kinase; and 4) other muscle endplate proteins. In addition to the profile of autoantibodies, MG may be classified according the location of the affected muscles (ocular vs generalized), the age of symptom onset, and the nature of thymic pathology. Immunopathologic events leading to the production of autoantibodies differ in the various disease subtypes. Advances in our knowledge of the immunopathogenesis of the subtypes of MG will allow for directed utilization of the ever-growing repertoire of therapeutic agents that target distinct nodes in the immune pathway relevant to the initiation and maintenance of autoimmune disease. In this review, we examine the pathogenesis of MG subtypes, current treatment options, and emerging new treatments and therapeutic targets.

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Section: Mg Subtypesmentioning

confidence: 99%

Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis

2016

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“…Thymectomy does appear to have a positive impact in double-seronegative patients (7), an observation that may reflect the likelihood that many of these patients actually harbor anti-acetylcholine receptor antibodies when tested with cell-based assays that cluster the receptor, mimicking the architecture of the postsynaptic membrane (9,10). In most reports, thymectomy in MuSK-antibody positive patients seems to have little if any favorable impact (7,8), providing further emphasis to the need to individualize management approaches for patients with MG.…”

Section: To the Editormentioning

confidence: 99%

Randomized Trial of Thymectomy in Myasthenia Gravis

2016

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“…They were able to show that transfer of these IgG1 antibodies into mice reduced miniature endplate potentials to an extent similar to AChR antibodies. 22 While testing for AChR and MuSK antibodies remains the mainstay of diagnostic testing in MG and detects antibodies in around 90% of patients with generalized MG, testing for Lrp4 or clustered AChR antibodies may increase the sensitivity of MG antibody testing to .95% in the near future. DISCUSSION Advancement in our understanding and treatment of MG has transformed this once debilitating disease into one of the most treatable neuromuscular disorders.…”

Section: New Antibody Testingmentioning

confidence: 99%

Myasthenia gravis

Statland

Ciafaloni

2013

Neur Clin Pract

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SummaryMyasthenia gravis (MG) is the most common autoimmune disease affecting neuromuscular junction transmission. MG is characterized by muscle weakness that worsens with activity and fluctuates over the course of the day. Involvement of respiratory musculature can lead to life-threatening crisis requiring intensive care unit care. Antibody testing is positive in most patients with MG. Treatment of MG includes short-term symptomatic treatment, chronic immunosuppression, surgical intervention, and immunomodulatory therapies for severe disease or crisis. We review advances in 5 areas relevant to diagnosis and management of MG: the role of IV immunoglobulin vs plasmapharesis in myasthenic crisis and severe disease; the clinical characterization of patients with antibodies to muscle-specific tyrosine kinase receptors; old and new investigational treatments; management of MG in pregnancy; and new confirmatory diagnostic tests. M yasthenia gravis (MG) is the most commonly encountered autoimmune disease of the neuromuscular junction with an estimated worldwide prevalence between 15 and 179 per million people. MG causes fluctuating weakness that worsens with activity and as the day progresses, and ocular weakness, causing ptosis and diplopia.1 In 15% of patients, life-threatening respiratory weakness can occur, called myasthenic crisis. Ocular symptoms are the most common presenting symptoms, with around two-thirds of patients progressing to generalized disease, usually within the first 2 years. The diagnosis is based on clinical history and neurologic examination and confirmed by electrodiagnostic testing and the presence of serum autoantibodies directed at proteins in the neuromuscular junction. The vast majority of patients with generalized MG (;85%) and pure ocular MG (;50%) will have antibodies to the skeletal muscle nicotinic acetylcholine receptor (AChR). An additional 8%-10% of patients with generalized disease have antibodies to muscle-specific tyrosine kinase receptor (MuSK), an enzyme involved in acetylcholine receptor clustering in the synaptic cleft.

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Presence and Pathogenic Relevance of Antibodies to Clustered Acetylcholine Receptor in Ocular and Generalized Myasthenia Gravis

Cited by 129 publications

References 24 publications

Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis

Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis

Randomized Trial of Thymectomy in Myasthenia Gravis

Myasthenia gravis

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