Suppression of development of experimental autoimmune myasthenia gravis with isogeneic monoclonal antiidiotopic antibody

We have made use of isogeneic anti-idiotopic (anti-Id) monoclonal antibodies (mAb) to modify experimental autoimmune myasthenia gravis (EAMG) in Lewis rats. High-avidity anti-Id mAb HC-4A (Kd = 0.1 nM) and HC-29 (Kd = 0.1 nM) were produced against an anti-acetylcholine receptor (anti-AChR) Lewis-rat mAb 132A (Kd = 0.34 nM) that is capable of inducing passive-transfer EAMG. mAb HC-4A and HC-29 define separate framework Id cross-reactive with anti-AChR mAb recognizing different AChR epitopes. Animals were preinjected i.p. with either anti-Id mAb or with control mAb and then were actively immunized 2 wk later with purified AChR. All animals had elevated total serum anti-AChR antibody titers, despite the absence of weakness or decremental electromyographic findings. Animals preinjected with control mAb developed serum anti-AChR titers of 1.34 ± 0.29 μM (mean ± SEM) and reduced muscle AChR content to 30 percent of normal. Animals injected with 0.5 mg/kg of either anti-Id had significantly lower serum anti-AChR titers, 0.55 ± 0.1, p<0.05, and normal muscle AChR content. Both the 132A Id and the anti-Id complementary to 132A were detected in the serum of all of the animals preinjected with this dose of either anti-Id HC-29 or HC-4A, whereas both were detected in a much smaller percentage of the animals receiving control mAb. These results show that pretreatment with anti-Id not only perturbs this Id-anti-Id network, but also suppresses the overall polyclonal anti-AChR response with resultant protection of actively immunized animals from EAMG.