Direct proof of the in vivo pathogenic role of the AChR autoantibodies from myasthenia gravis patients.

Several studies have suggested that the autoantibodies (autoAbs) against muscle acetylcholine receptor (AChR) of myasthenia gravis (MG) patients are the main pathogenic factor in MG; however, this belief has not yet been confirmed with direct observations. Although animals immunized with AChR or injected with anti-AChR monoclonal Abs, or with crude human MG Ig fractions exhibit MG symptoms, the pathogenic role of isolated anti-AChR autoAbs, and, more importantly, the absence of pathogenic factor(s) in the autoAb-depleted MG sera has not yet been shown by in vivo studies. Using recombinant extracellular domains of the human AChR α and β subunits, we have isolated autoAbs from the sera of four MG patients.

Anti-MuSK- and anti-AChR-positive myasthenia gravis induced by d-penicillamine.

Background: Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction usually caused by antibodies to the nicotinic acetylcholine receptor (AChR) and occasionally to muscle-specific kinase (MuSK). D-penicillamine is a therapeutic agent for several diseases, but can also induce a number of immune-mediated disorders, including MG, as a side-effect. In most patients with D-penicillamine-induced MG, anti-AChR antibodies are detected, but the presence of anti-MuSK antibodies has not been reported previously.

Recent approaches to the development of antigen-specific immunotherapies for myasthenia gravis.

Acquired autoimmune myasthenia gravis (MG) is the most common disease that affects the neuromuscular junction (NMJ). MG is associated with autoantibodies (auto-Abs) to components of the NMJ. About 85-90% of MG patients have auto-Abs against the muscle nicotinic acetylcholine receptor (AChR), while about half of the remaining patients have auto-Abs against muscle-specific kinase.

Towards antigen-specific apheresis of pathogenic autoantibodies as a further step in the treatment of myasthenia gravis by plasmapheresis.

Myasthenia gravis (MG), a prototypic antibody-mediated autoimmune disease, presents an excellent target for scientific research aimed at a better understanding of the disease itself and the source that triggers an autoimmune reaction in an organism. MG is a neuromuscular disease caused mainly by an autoimmune response against the nicotinic acetylcholine receptor (AChR) which interferes with neuromuscular transmission. This review focuses on our studies on the extracellular domains of human muscle AChR subunits in an effort to develop an approach for the specific therapeutic apheresis of autoantibodies from patients' sera using the immobilized subunits as immunoadsorbents.

Isolation and functional characterization of anti-acetylcholine receptor subunit-specific autoantibodies from myasthenic patients: receptor loss in cell culture.

The muscle nicotinic acetylcholine receptor (nAChR) is the major autoantigen in the autoimmune disease myasthenia gravis (MG), in which autoantibodies bind to, and cause loss of, nAChRs. Antibody-mediated nAChR loss is caused by the action of complement and by the acceleration of nAChR internalization caused by antibody-induced cross-linking of nAChR molecules (antigenic modulation). To obtain an insight into the role of the various anti-nAChR antibody specificities in MG, we have studied nAChR antigenic modulation caused by isolated anti-subunit autoantibodies.