Use of monoclonal antiacetylcholine receptor antibodies to investigate the macrophage inflammation of acute experimental myasthenia gravis: refractoriness to a second episode of acute disease.

Abstract

The acute phase of experimental autoimmune myasthenia gravis (EAMG) is characterized by macrophage inflammation of muscle endplates and by muscle fiber necrosis. We induced acute EAMG by passive transfer of monoclonal antibodies (mAbs) directed against the acetylcholine receptor (AChR) to investigate this brief and self-limited disorder. After the initial acute phase, animals were refractory to induction of a second episode by subsequent injection of the same mAb, or another anti-AChR mAb of different idiotype and which binds to a separate epitope. Therefore, the refractory state was not caused by an anti-idiotypic response or epitopic modulation. Adoptive transfer of spleen cells from refractory animals had no effect, excluding a role of suppressor lymphocytes, and there was no evidence from experiments involving adoptive transfer of spleen cells from naive animals to refractory animals that refractory animals lacked effector cells.