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 acids 61-76, of the alpha chain of the acetylcholine 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 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.
Department of Physiology and Biophysics, University of Alabama at Birmingham 35294-0005.
S
S
Araga
R D
RD
LeBoeuf
J E
JE
Blalock
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D004557:Electric Organ / Q000378:metabolism; D005260:Female; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000276:immunology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology* / Q000302:isolation & purification; D014101:Torpedo
D010446:Peptide Fragments; D011950:Receptors, Cholinergic