scholarly journals Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1513 ◽  
Author(s):  
William D. Phillips ◽  
Angela Vincent
Keyword(s):  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Respiratory Muscles ◽  
Postsynaptic Membrane ◽  
Synaptic Function ◽  
Density Lipoprotein Receptor ◽  
Synapse Maintenance ◽  
Muscle Groups

Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (Ig)G1 and IgG3 antibodies to the acetylcholine receptor (AChR). They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4), are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms.

scholarly journals Autoantibodies to Low-Density Lipoprotein Receptor-Related Protein 4 in Double Seronegative Myasthenia Gravis: A Systematic Review

2017 ◽  
Vol 45 (1) ◽  
pp. 62-67 ◽  
Author(s):  
Stephen Bacchi ◽  
Philippe Kramer ◽  
Colin Chalk
Keyword(s):  
Myasthenia Gravis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Small Sample ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Related Protein ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor ◽  
Lipoprotein Receptor Related Protein

AbstractBackground: Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction in which a clinical diagnosis may be confirmed with serological testing. The most common autoantibodies used to support a diagnosis of MG are anti-acetylcholine receptor antibodies and anti-muscle-specific tyrosine kinase antibodies. In cases in which both of these autoantibodies are negative (termed double-seronegative [dSNMG]), other autoantibodies such as low-density lipoprotein receptor-related protein 4 (LRP4) may be used to aid in diagnosis. Methods: We have undertaken a systematic literature review to identify studies that have assessed the frequency of anti-LRP4 antibodies in dSNMG patients and the characteristics of anti-LRP4+ dSNMG patients (epidemiology, clinical features, electromyographic findings, or management). PubMed, EMBASE, Medline, and Scopus were searched on January 14, 2017, using the medical subject headings “myasthenia gravis” and “low-density lipoprotein receptor-related protein 4” or “LRP4.” Results: The initial search identified 367 articles. Fourteen publications met the inclusion criteria. There were ten cross-sectional research studies, three were case series, and one was a case report. The majority of studies were limited by small sample sizes of LRP4+ dSNMG. There has been a wide range of frequencies of anti-LRP4 antibodies detected in different MG patient populations, some involving different laboratory techniques. Conclusions: LRP4+ dSNMG is more likely than LRP4– dSNMG to have a younger onset of disease and occur in females. LRP4+ dSNMG most often is mild in severity and often involves isolated ocular weakness. It typically responds well to pyridostigmine or prednisone.

scholarly journals Myasthenia Gravis: Pathogenic Effects of Autoantibodies on Neuromuscular Architecture

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 671 ◽  
Author(s):  
Inga Koneczny ◽  
Ruth Herbst
Keyword(s):  
Myasthenia Gravis ◽  
Low Density Lipoprotein ◽  
Treatment Strategies ◽  
Density Lipoprotein ◽  
Clinical Aspects ◽  
Pathogenic Mechanisms ◽  
Skeletal Muscle Weakness ◽  
Density Lipoprotein Receptor ◽  
Muscle Specific Kinase ◽  
And Function

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ). Autoantibodies target key molecules at the NMJ, such as the nicotinic acetylcholine receptor (AChR), muscle-specific kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (Lrp4), that lead by a range of different pathogenic mechanisms to altered tissue architecture and reduced densities or functionality of AChRs, reduced neuromuscular transmission, and therefore a severe fatigable skeletal muscle weakness. In this review, we give an overview of the history and clinical aspects of MG, with a focus on the structure and function of myasthenic autoantigens at the NMJ and how they are affected by the autoantibodies’ pathogenic mechanisms. Furthermore, we give a short overview of the cells that are implicated in the production of the autoantibodies and briefly discuss diagnostic challenges and treatment strategies.

Sign in / Sign up

Export Citation Format

Share Document