Intrathymic expression of neuromuscular acetylcholine receptors and the immunpathogenesis of myasthenia gravis.

The thymus has been considered to play an important role in the pathogenesis of myasthenia gravis (MG), an autoimmune disease characterized by skeletal muscle weakness. However, the pathogenic role of the thymus still remains a mystery. The neuromuscular type of acetylcholine receptor (AChR) was the first self-protein associated with a defined autoimmune disease that was found to be expressed by thymic stromal populations. The studies described herein represent our efforts to determine how this "promiscuous" autoantigen expression may be involved in the immunopathogenesis of MG. We review our work, characterizating the expression of the alpha subunit of AChR (AChRalpha) in the thymus, and advance a new hypothesis that examines the intrathymic expression of this autoantigen in disease pathogenesis.