MYASTHENIA-GRAVIS SERA CONTAINING ANTIRYANODINE RECEPTOR ANTIBODIES INHIBIT BINDING OF [H-3]-RYANODINE TO SARCOPLASMIC-RETICULUM

Myasthenia gravis (MG) patients with thymoma often have antibodies aga inst the calcium-release channel of the sarcoplasmic reticulum (SR) in striated muscle, the ryanodine receptor (RyR). RyR function can be te sted in vitro by measuring the degree of [H-3]-ryanodine binding to SR . In this study, sera from 9 out of 14 MG patients containing RyR anti bodies inhibited [H-3]-ryanodine binding to SR membranes from rat skel etal muscle. The 9 patients with antibodies inhibiting ryanodine bindi ng had more severe MG than those with noninhibiting antibodies (P = 0. 006), Sera from MG patients with acetylcholine receptor and titin musc le antibodies but no antibodies against RyR and blood-donor sera did n ot have an inhibiting effect in the [H-3]-ryanodine binding assay. The results show that RyR antibodies in MG patients have high affinity fo r the RyR, and that the binding of antibodies probably affects calcium release from SR by locking the RyR ion channel in a closed position. (C) 1998 John Wiley & Sons, Inc.