PMID- 18567857
OWN - NLM
STAT- MEDLINE
DCOM- 20080908
LR  - 20211020
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 1132
DP  - 2008
TI  - Myasthenia gravis seronegative for acetylcholine receptor antibodies.
PG  - 84-92
LID - 10.1196/annals.1405.020 [doi]
AB  - 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.
FAU - Vincent, Angela
AU  - Vincent A
AD  - Neurosciences Group, Weatherall Institute of Molecular Medicine and Department of 
      Clinical Neurology, John Radcliffe Hospital, Oxford, United Kingdom. 
      angela.vincent@imm.ox.ac.uk
FAU - Leite, Maria Isabel
AU  - Leite MI
FAU - Farrugia, Maria Elena
AU  - Farrugia ME
FAU - Jacob, Saiju
AU  - Jacob S
FAU - Viegas, Stuart
AU  - Viegas S
FAU - Shiraishi, Hiro
AU  - Shiraishi H
FAU - Benveniste, Olivier
AU  - Benveniste O
FAU - Morgan, B Paul
AU  - Morgan BP
FAU - Hilton-Jones, David
AU  - Hilton-Jones D
FAU - Newsom-Davis, John
AU  - Newsom-Davis J
FAU - Beeson, David
AU  - Beeson D
FAU - Willcox, Nick
AU  - Willcox N
LA  - eng
GR  - G117/490/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Antibodies)
RN  - 0 (Receptors, Cholinergic)
RN  - EC 2.7.10.1 (MUSK protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Antibodies/blood/*immunology
MH  - Electrophysiology
MH  - Humans
MH  - Myasthenia Gravis/epidemiology/*immunology/*metabolism/pathology
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Receptors, Cholinergic/*immunology/*metabolism
EDAT- 2008/06/24 09:00
MHDA- 2008/09/09 09:00
CRDT- 2008/06/24 09:00
PHST- 2008/06/24 09:00 [pubmed]
PHST- 2008/09/09 09:00 [medline]
PHST- 2008/06/24 09:00 [entrez]
AID - 1132/1/84 [pii]
AID - 10.1196/annals.1405.020 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2008;1132:84-92. doi: 10.1196/annals.1405.020.