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Passive transfer models of myasthenia gravis with muscle-specific kinase antibodies
- Source :
- Annals of the New York Academy of Sciences. 1413:111-118
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- Myasthenia gravis (MG) with antibodies to muscle-specific kinase (MuSK) is characterized by fluctuating fatigable weakness. In MuSK MG, involvement of bulbar muscles, neck, and shoulder and respiratory weakness are more prominent than in acetylcholine receptor (AChR) MG. MuSK autoantibodies are mainly of the IgG4 subclass, and as such are unable to activate complement, have low affinity for Fc receptors, and are functionally monovalent. Therefore, the pathogenicity of IgG4 MuSK autoantibodies was initially questioned. A broad collection of in vitro active immunization and passive transfer models has been developed that have shed light on the pathogenicity of MuSK autoantibodies. Passive transfer studies with purified IgG4 from MuSK MG patients confirmed that IgG4 is sufficient to reproduce clear clinical, electrophysiological, and histological signs of myasthenia. In vitro experiments revealed that MuSK IgG4 autoantibodies preferably bind the first Ig-like domain of MuSK, correlate with disease severity, and interfere with the association between MuSK and low-density lipoprotein receptor-related protein 4 and collagen Q. Some patients have additional IgG1 MuSK autoantibodies, but their role in the disease is unclear. Altogether, this provides a rationale for epitope-specific or IgG4-specific treatment strategies for MuSK MG and emphasizes the importance of the development of different experimental models.
- Subjects :
- 0301 basic medicine
biology
business.industry
Kinase
General Neuroscience
Autoantibody
Active immunization
medicine.disease
General Biochemistry, Genetics and Molecular Biology
Subclass
Myasthenia gravis
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
History and Philosophy of Science
Immunology
biology.protein
Medicine
Antibody
business
Receptor
030217 neurology & neurosurgery
Acetylcholine receptor
Subjects
Details
- ISSN :
- 00778923
- Volume :
- 1413
- Database :
- OpenAIRE
- Journal :
- Annals of the New York Academy of Sciences
- Accession number :
- edsair.doi...........c6a1d377f8931630fdefe465b6071923