Presence and Pathogenic Relevance of Antibodies to Clustered Acetylcholine Receptor in Ocular and Generalized Myasthenia Gravis Clustered AChR Antibodies in Myasthenia Gravis

Jacob S, Viegas S, Leite M, et al. — Wed, 01 Aug 2012 00:00:00 GMT

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.

Seronegative Myasthenia Gravis The Importance of Clusters of Acetylcholine Receptors Seronegative Myasthenia Gravis

Rowland LP. — Wed, 01 Aug 2012 00:00:00 GMT

In the current issue of the Archives, Jacob and colleagues update details of the pathogenesis of myasthenia gravis (MG), which may be the prototype of all human autoimmune diseases. The modern story could have started with John A. Simpson (1922-2009), a Scottish neurologist and pioneer in electromyography. He published 2 reviews that summarized the evidence.

JAMA Neurology: Myasthenia Gravis Topic Collection

Presence and Pathogenic Relevance of Antibodies to Clustered Acetylcholine Receptor in Ocular and Generalized Myasthenia Gravis Clustered AChR Antibodies in Myasthenia Gravis

Seronegative Myasthenia Gravis The Importance of Clusters of Acetylcholine Receptors Seronegative Myasthenia Gravis