title: Modeling the intrathymic pathogenesis of myasthenia gravis.
abstract: Myasthenia gravis is (MG) a prototypic autoimmune disease; the immune effector mechanisms and autoantigenic target have been delineated. However, the events that lead to the abrogation of self-tolerance to neuromuscular acetylcholine receptors (nAChRs) remain a mystery. The thymus gland has long been considered to hold the key to solving this mystery, although the nature of its involvement remains to be elucidated. The nAChR was one of the first self-proteins associated with a defined autoimmune disease that was found to be expressed on 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, characterizing the expression of the nAChR alpha subunit in the thymus, and advance a hypothesis and experimental model, which explore how intrathymic expression of this autoantigen may contribute to the immunopathogenesis of this autoimmune disease.
authors: Allergy and Immunology Section, Perelman School of Medicine at The University of Pennsylvania, 316 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, United States. Electronic address: frog@mail.med.upenn.edu.
authors: Arnold I
authors: AI
authors: Levinson
mesh_terms: D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D018448:Models, Immunological; D009157:Myasthenia Gravis / Q000276:immunology* / Q000473:pathology*; D021122:Protein Subunits / Q000276:immunology / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology*
chemical_list: D001324:Autoantigens; D021122:Protein Subunits; D011978:Receptors, Nicotinic
keywords: Acetylcholine receptor; Experimental model; Inflammation; Myasthenia gravis; Thymus