Myasthenia Gravis Seronegative for Acetylcholine Receptor Antibodies

Antibodies to muscle‐specific kinase (MuSK) are found in a variable proportion of patients with myasthenia without typical acetylcholine receptor (AChR) antibodies, but their characteristics and pathogenic mechanisms are not fully understood. We discuss the incidence and pathogenicity of MuSK antibo...

Full description

Saved in:
Bibliographic Details
Published in:Annals of the New York Academy of Sciences 2008-06, Vol.1132 (1), p.84-92
Main Authors: Vincent, Angela, Leite, Maria Isabel, Farrugia, Maria Elena, Jacob, Saiju, Viegas, Stuart, Shiraishi, Hiro, Benveniste, Olivier, Morgan, B. Paul, Hilton-Jones, David, Newsom-Davis, John, Beeson, David, Willcox, Nick
Format: Article
Language:English
Subjects:
acetylcholine receptor
animal model
Animals
Antibodies - blood
Antibodies - immunology
complement
Electrophysiology
Humans
IgG subclass
immunoglobulin G
muscle-specific kinase
myasthenia gravis
Myasthenia Gravis - epidemiology
Myasthenia Gravis - immunology
Myasthenia Gravis - metabolism
Myasthenia Gravis - pathology
Receptor Protein-Tyrosine Kinases - metabolism
Receptors, Cholinergic - immunology
Receptors, Cholinergic - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Antibodies to muscle‐specific kinase (MuSK) are found in a variable proportion of patients with myasthenia without typical acetylcholine receptor (AChR) antibodies, but their characteristics and pathogenic mechanisms are not fully understood. We discuss the incidence and pathogenicity of MuSK antibodies and how clinical studies, animal models, and cultured cell lines can be used to elucidate their pathogenic mechanisms. Patients without either AChR or MuSK antibodies (seronegative myasthenia) appear to present another disease subtype that is highly similar to that of typical myasthenia gravis. We demonstrate a new method that detects AChR antibodies in these patients and show that these low‐affinity AChR antibodies are predominantly IgG1 and can activate complement C3b deposition. Similarly MuSK antibodies, although mainly IgG4, are partially IgG1 and can activate C3b deposition. Overall, these results suggest that complement‐activation may be an important pathogenic mechanism even in patients without conventional AChR antibodies.
ISSN:0077-8923
1749-6632
DOI:10.1196/annals.1405.020