Barchan_1999_Proc.Natl.Acad.Sci.U.S.A_96_8086

Reference

Title : Antigen-specific modulation of experimental myasthenia gravis: nasal tolerization with recombinant fragments of the human acetylcholine receptor alpha-subunit - Barchan_1999_Proc.Natl.Acad.Sci.U.S.A_96_8086
Author(s) : Barchan D , Souroujon MC , Im SH , Antozzi C , Fuchs S
Ref : Proc Natl Acad Sci U S A , 96 :8086 , 1999
Abstract :

Myasthenia gravis (MG) and experimental autoimmune myasthenia gravis (EAMG) are antibody-mediated autoimmune diseases in which the nicotinic acetylcholine receptor (AcChoR) is the major autoantigen. The immune response in these diseases is heterogeneous and is directed to a wide variety of T and B cell epitopes of AcChoR. Candidate molecules for specific immunotherapy of MG should, therefore, have a broad specificity. We used recombinant fragments of the human AcChoR, encompassing the extracellular domain of the alpha-subunit, or shorter fragments derived from it, in experiments to modulate EAMG. We have demonstrated that intranasal administration of these recombinant fragments, which represent a major portion of epitopes involved in MG, prevents the induction of EAMG in rats and immunosuppresses an ongoing disease, as assessed by clinical symptoms, weight loss, and muscle AcChoR content. These effects on EAMG were accompanied by a marked reduction in the proliferative T-cell response and IL-2 production in response to AcChoR, in reduced anti-self AcChoR antibody titers and in an isotype switch of AcChoR-specific antibodies, from IgG2 to IgG1. We conclude that nasal tolerance induced by appropriate recombinant fragments of human AcChoR is effective in suppressing EAMG and might possibly be considered as a therapeutic modality for MG.

PubMedSearch : Barchan_1999_Proc.Natl.Acad.Sci.U.S.A_96_8086
PubMedID: 10393952

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Citations formats

Barchan D, Souroujon MC, Im SH, Antozzi C, Fuchs S (1999)
Antigen-specific modulation of experimental myasthenia gravis: nasal tolerization with recombinant fragments of the human acetylcholine receptor alpha-subunit
Proc Natl Acad Sci U S A 96 :8086

Barchan D, Souroujon MC, Im SH, Antozzi C, Fuchs S (1999)
Proc Natl Acad Sci U S A 96 :8086