title: Suppression of ongoing experimental myasthenia by oral treatment with an acetylcholine receptor recombinant fragment.
abstract: Myasthenia gravis (MG) is an autoimmune disorder in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. In an attempt to develop an antigen-specific therapy for MG, we administered a nonmyasthenogenic recombinant fragment of AChR orally to rats. This fragment, corresponding to the extracellular domain of the human AChR alpha-subunit (Halpha1-205), protected rats from subsequently induced experimental autoimmune myasthenia gravis (EAMG) and suppressed ongoing EAMG when treatment was initiated during either the acute or chronic phases of disease. Prevention and suppression of EAMG were accompanied by a significant decrease in AChR-specific humoral and cellular responses. The underlying mechanism for the Halpha1-205-induced oral tolerance seems to be active suppression, mediated by a shift from a T-helper 1 (Th1) to a Th2/Th3 response. This shift was assessed by changes in the cytokine profile, a deviation of anti-AChR IgG isotypes from IgG2 to IgG1, and a suppressed AChR-specific delayed-type hypersensitivity response. Our results in experimental myasthenia suggest that oral administration of AChR-specific recombinant fragments may be considered for antigen-specific immunotherapy of myasthenia gravis.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: S H
authors.initials: SH
authors.lastname: Im
authors.forename: D
authors.initials: D
authors.lastname: Barchan
authors.forename: S
authors.initials: S
authors.lastname: Fuchs
authors.forename: M C
authors.initials: MC
authors.lastname: Souroujon
mesh_terms: D000284:Administration, Oral; D000818:Animals; D005260:Female; D007108:Immune Tolerance; D009157:Myasthenia Gravis / Q000628:therapy*; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D010446:Peptide Fragments; D011950:Receptors, Cholinergic; D011994:Recombinant Proteins; D010047:Ovalbumin