Antibodies from patients with myasthenia gravis recognize determinants unique to extrajunctional acetylcholine receptors.

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Abstract
The interaction was studied between sera from patients with myasthenia gravis and acetylcholine receptor (AcChoR) purified from normal and denervated rat skeletal muscles [junctional receptor (JR) and extrajunctional receptor (EJR), respectively]. Of 10 myasthenic sera, 8 had titers against EJR that were significantly higher (1.1-2.4 times) than their titers against JR. The anti-receptor titers of these sera ranged from 2-102 nM. Although activities of 3 other sera were too low (< 1 nM) to allow accurate titrations, provisional measurements with these sera gave titers against EJR that were at least as high (1.0-1.4 times) as those against JR. Competition experiments with myasthenic sera demonstrated 2 classes of determinants on rat AcChoR: those that are common to JR and EJR and those that are present or exposed only on EJR. Myasthenic sera did not recognize any determinants unique to JR. Several antisera raised to purified AcChoR from eel or Torpedo electric organs or denervated rat skeletal muscle had equal titers against the 2 forms of receptor. Treatment of JR and EJR by various enzymatic or chemical procedures designed to alter prosthetic groups on the proteins failed to affect their antigenic reactivity. AcChoR from embryonic rats was indistinghishable immunologically from EJR of adult muscle.