Suppression of ongoing experimental myasthenia by oral treatment with an acetylcholine receptor recombinant fragment
Sin-Hyeog Im, … , Sara Fuchs, Miriam C. Souroujon
Sin-Hyeog Im, … , Sara Fuchs, Miriam C. Souroujon
Published December 15, 1999
Citation Information: J Clin Invest. 1999;104(12):1723-1730. https://doi.org/10.1172/JCI8121.
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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 α-subunit (Hα1-205), 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 Hα1-205–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

Sin-Hyeog Im, Dora Barchan, Sara Fuchs, Miriam C. Souroujon

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Exogenous IL-2 does not restore the suppressed T-cell response. AChR-spe...
Exogenous IL-2 does not restore the suppressed T-cell response. AChR-specific lymphocyte proliferation of rats treated by Hα1-205 or OVA at the acute phase of EAMG was measured before (a) and after a 5-day culture in the absence (b) or presence (c) of rat rIL-2. Results are expressed as mean stimulation index (counts per minute incorporated by stimulated cells per counts per minute incorporated by unstimulated cells). Biologic activity of rIL-2 was verified by the proliferative response of the CTLL cell line. Representative of 3 independent experiments. *P < 0.005.