The acetylcholine receptor (AChR) is the major autoantigen in the antibody-mediated disease myasthenia gravis (MG) and its animal model experimental autoimmune myasthenia gravis (EAMG). This study demonstrates that rats immunized with a recombinant fragment corresponding to the normally exposed extracellular region of the rat AChR α-subunit first develop antibodies to the injected extracellular portion only, but later develop antibodies to intracellular cytoplasmic epitopes of AChR. The presence of autoantibodies to intracellular epitopes seems to be correlated with development of clinical signs of disease. We propose that a similar process of epitope spreading may take place in the natural course of myasthenia.
Bibliographical noteFunding Information:
This research was supported by grants from The Muscular Dystrophy Association of America (MDA), The Association Francaise Contre les Myopathies (AFM), The EC (No's QLG1-CT-2001-10918, QLRT-2001-00225), The Abramson Family Foundation and the Wood-Byer Foundation.
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- Acetylcholine receptor
- Determinant spreading
- Myasthenia gravis