PREVENTION OF EXPERIMENTAL AUTOIMMUNE MYASTHENIA-GRAVIS BY MANIPULATION OF THE IMMUNE NETWORK WITH A COMPLEMENTARY PEPTIDE FOR THE ACETYLCHOLINE-RECEPTOR

Myasthenia gravis (MG) and experimental autoimmune myasthenia gravis (EAMG) are caused, in part, by the production of autoantibodies against the main immunogenic region, amino adds 61-76, of the alpha chain of the acetycholine receptor (AChR). Theoretically, induction of anti-idiotypic (Id) antibodies (Abs) should be a highly specific treatment for the disease by virtue of their potential ability to neutralize Abs to the AChR. We have tested this idea by attempting to evoke such anti-Id Abs by immunization with a peptide (termed RhCA 67-16) encoded by RNA complementary to the Torpedo AChR main immunogenic region and determining whether such treatment will prevent the development of EAMG. Immunization with RhCA 67-16, but not a control peptide termed PBM 9-1, was found to elicit the production of anti-Id Abs that blocked recognition of native Torpedo AChR by its Ab. This anti-Id Ab activity was ablated by incubation of the anti-RhCA 67-16 serum with RhCA 67-16, but not PBM 9-1, prior to the assay for Ab binding to AChR. The anti-Id Ab-inducing activity of RhCA 67-16 was confirmed by the ability to produce a rat monoclonal Ab to RhCA 67-16 that showed anti-Id activity for polyclonal rat Ab reactive with AChR residues 67-76. Most importantly, RhCA 67-16 immunization also prevented the development of EAMG in Lewis rats challenged with Torpedo AChR (25% incidence versus 90% in the controls) and diminished the AChR Ab levels in animals injected with low doses of AChR. Our results suggest a therapy for MG and perhaps other autoimmune diseases through the induction of anti-Id Abs by peptide immunogens.