Acetylcholine receptor–specific immunosuppressive therapy of experimental autoimmune myasthenia gravis and myasthenia gravis

Experimental autoimmune myasthenia gravis (EAMG) and myasthenia gravis (MG) are caused by autoantibodies to the extracellular domain of muscle nicotinic acetylcholine receptors (AChRs). Autoantibodies to the cytoplasmic domain of AChRs do not cause EAMG because they cannot bind AChRs in vivo. The ideal MG therapy would quickly and permanently suppress only the pathological autoimmune response to AChRs. We have developed a specific immunosuppressive therapy for EAMG that involves immunizing rats with bacterially expressed cytoplasmic domains of human muscle AChRs. Therapy prevents onset of chronic EAMG, rapidly suppresses ongoing EAMG, and is potent, robust, long lasting, and safe, because the therapeutic antigen cannot induce EAMG. The therapy was developed using incomplete Freund's adjuvant, but is likely to work equally well with alum adjuvants routinely used for human immunizations. Therapeutic mechanisms may involve a combination of antibody-mediated feedback suppression and regulatory T and/or B lymphocytes.