Oral tolerance in myasthenia gravis.
Because of the antibody-mediated pathogenesis of MG, it is of particular interest to understand the effects of oral administration of the autoantigen AChR on the disease process. It is now clear that feeding AChR prior to immunization can prevent clinical manifestation of EAMG. It initially primed, then inhibited, antibody responses to foreign (Torpedo) AChR and self (rat) AChR, with a delayed onset. Cellular responses to AChR, evaluated by lymphocyte proliferation and IL-2 production, were markedly inhibited. The effects were dependent on the dose and purity of the fed antigen. Tolerance to an orally administered unrelated antigen, OVA, was more prompt in development and more profound, illustrating the influence of the nature of the antigen on tolerance. The tolerance induced was antigen specific. Oral administration of AChR after immunization resulted in inhibition of the clinical manifestation of EAMG, concomitant with a paradoxical enhancement of the AChR-antibody responses. Both the clinical benefit and the antibody response appear to be dependent on the feeding protocol. These findings suggest that a molecule with less immunogenic potential than native AChR may be required for safe and effective oral treatment of ongoing disease.
Drachman
D B
DB
Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21287-7519, USA.
Okumura
S
S
Adams
R N
RN
McIntosh
K R
KR
D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy; D009157:Myasthenia Gravis / Q000276:immunology* / Q000628:therapy*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D001324:Autoantigens; D011950:Receptors, Cholinergic; D010047:Ovalbumin