Journal of Neuroimmunology, 37 (1992) 1-7 1 © 1992 Elsevier Science Publishers B.V. All rights reserved 0165-5728/92/$05.00 JN1 02121 Myasthenia gravis patients with a thymoma have antibodies against a high molecular weight protein in sarcoplasmic reticulum A. Mygland ~,b, O.-B. Tysnes a, J.A. Aarli a, P.R. Flood c and N.E. Gilhus " a Department of Neurology, b Broegelmann Research Laboratory for Microbiology, and '" Department of Anatomy, Unicersity of Bergen, Bergen, Norway (Received 28 June 1991) (Revised, received 27 September 1991) (Accepted 27 September 1991) Key words: Myasthenia gravis; Thymoma; Sarcoplasmic rcticulum; Autoantibody Summary Our purpose was to investigate whether components of the sarcoplasmic reticulum (SR) are relevant antigens in myasthenia gravis (MG). Using enzyme-linked immunosorbent assay (ELISA), 75 MG sera and 120 control sera were examined for IgG antibodies against SR prepared from rabbit skeletal muscle. 16/30 thymoma MG patients had IgG antibodies that reacted with SR. 1/30 MG patients with thymic hyperplasia and 3/15 MG patients with thymic atrophy had SR antibodies in low concentrations. Control sera were negative. Using immunobiot, SR antibodies were detected in the thymoma group only. 14/30 sera from thymoma patients reacted with a protein of 320 kDa relative molecular weight. The only reported SR protein with similar electrophoretic mobility is the subunit of the spanning protein which links junctional SR to sarcolemma and functions as a calcium-release channel. Introduction The abnormal muscular fatiguability in myas- thenia gravis (MG) is mainly due to an impaired neuromuscular transmission caused by autoanti- bodies to the nicotinic acetylcholine receptor (AChR) (Drachman et al., 1980). Some MG pa- tients, including almost all with a thymoma, have in addition antibodies against other components of the muscle cell (Strauss et al., 1965; Penn et al., 1986). These skeletal muscle antibodies are apparently heterogenous, giving various cross- Correspondence to: Dr..~se Mygland, Department of Neurology, Haukeland Hospital, 5021 Bergen, Norway. striational patterns by immunofluorescent stain- ing (Peers et al., 1976). They are reported to react with actin, myosin, a-actinin (Williams and Lennon, 1986; Ohta et al., 1990) and titin (Aarli et al., 1990). Much less attention has been paid to the reac- tivity of MG sera with non-myofibrillary muscle proteins. Electron microscopic studies have shown binding of MG sera to membranes of the sar- coplasmic reticulum (SR) (Mendell et al., 1973; Flood et al., 1987), but the relevant membrane- associated antigens have not been identified. The possibility of SR as a relevant immunogen in MG gained more functional interest when a study of Pagala et al. (1990) showed that some MG patients have electromyographic signs of im-