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Presence and Pathogenic Relevance of Antibodies to Clustered Acetylcholine Receptor in Ocular and Generalized Myasthenia GravisClustered AChR Antibodies in Myasthenia Gravis.
MedLine Citation:
PMID:  22689047     Owner:  NLM     Status:  Publisher    
BACKGROUND Clustered acetylcholine receptor antibodies (clustered AChR-Abs) have been detected in a proportion of patients with previously "seronegative" (SN) generalized myasthenia gravis (GMG), but their presence in patients with ocular MG (OMG) and their pathogenicity in vivo are unknown. OBJECTIVE To test the presence of clustered AChR-Abs and their pathophysiologic properties in patients with SNMG. DESIGN Screening and diagnostic tests. SETTING Regional specialist myasthenia center and clinical laboratory. PATIENTS Serum samples from 16 patients with SN and OMG were tested for binding to clustered AChRs. Results from 28 further SN patients (14 OMG) were correlated with their single fiber electromyography values. MAIN OUTCOME MEASURES Presence, complement-fixation capacity, correlation with neurophysiologic changes, and in vivo pathogenicity of clustered AChR-Abs. RESULTS Up to 50% of patients with previous SN-OMG had complement-fixing IgG1 clustered AChR-Abs. IgG binding (n = 28) and complement deposition (n = 21) each correlated with the mean consecutive difference (jitter) on single-fiber electromyography. Injection of purified IgG from 2 patients with clustered AChR-Abs into wild-type or complement regulator-deficient mice reduced miniature end plate potential amplitudes to an extent similar to that found with AChR-Abs, and complement was deposited at the end plates. A trend was noted toward an increase in the number of packets of acetylcholine released (quantal content). CONCLUSIONS A proportion of patients with SN-GMG or OMG have clustered AChR-Abs that correlate with their electrophysiologic features. Clustered AChR-Abs can passively transfer disease to mice, demonstrating their pathogenicity, and the mechanisms seem similar to those of patients with typical AChR-Abs.
Saiju Jacob; Stuart Viegas; Maria Isabel Leite; Richard Webster; Judith Cossins; Robin Kennett; David Hilton-Jones; B Paul Morgan; Angela Vincent
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-11
Journal Detail:
Title:  Archives of neurology     Volume:  -     ISSN:  1538-3687     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372436     Medline TA:  Arch Neurol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  1-8     Citation Subset:  -    
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