Antibodies in myasthenia gravis and related disorders.
Acetylcholine receptor (AChR) antibodies are present in around 85% of patients with myasthenia gravis (MG) as measured by the conventional radioimmunoprecipitation assay. Antibodies that block the fetal form of the AChR are occasionally present in mothers who develop MG after pregnancy, especially in those whose babies are born with arthrogryposis multiplex congenita. The antibodies cross the placenta and block neuromuscular transmission, leading to joint deformities and often stillbirth. In these mothers, antibodies made in the thymus are mainly specific for fetal AChR and show restricted germline origins, suggesting a highly mutated clonal response; subsequent spread to involve adult AChR could explain development of maternal MG in those cases who first present after pregnancy. In the 15% of "seronegative" MG patients without AChR antibodies (SNMG), there are serum factors that increase AChR phosphorylation and reduce AChR function, probably acting via a different membrane receptor. These factors are not IgG and could be IgM or even non-Ig serum proteins. In a proportion of SNMG patients, however, IgG antibodies to the muscle-specific kinase, MuSK, are present. These antibodies are not found in AChR antibody-positive MG and are predominantly IgG4. MuSK antibody positivity appears to be associated with more severe bulbar disease that can be difficult to treat effectively.
Vincent
Angela
A
Neurosciences Group, Department of Clinical Neurology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom. angela.vincent@imm.ox.ac.uk
McConville
John
J
Farrugia
Maria Elena
ME
Bowen
John
J
Plested
Paul
P
Tang
Teresa
T
Evoli
Amelia
A
Matthews
Ian
I
Sims
Gary
G
Dalton
Paolo
P
Jacobson
Leslie
L
Polizzi
Agata
A
Blaes
Frans
F
Lang
Bethan
B
Beeson
David
D
Willcox
Nick
N
Newsom-Davis
John
J
Hoch
Werner
W
D000375:Aging; D000906:Antibodies / Q000145:classification / Q000378:metabolism; D001176:Arthrogryposis / Q000276:immunology; D001666:Binding Sites, Antibody; D005260:Female; D005326:Fetal Proteins / Q000276:immunology* / Q000378:metabolism; D005333:Fetus / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D009157:Myasthenia Gravis / Q000145:classification / Q000276:immunology*; D020294:Myasthenic Syndromes, Congenital / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology*; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D005326:Fetal Proteins; D007135:Immunoglobulin Variable Region; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases