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European Molecular Biology Laboratory (Drs. Gautel, Leonard, and Labeit, and A. Lakey, Z. Holmes, and S. Scales), Heidelberg, Germany; the Institute for Molecular Pathology (Dr. Barlow), Vienna, Austria; and the Department of Neurology (Drs. Mygland, Gilhus, and Aarli), University of Bergen, Haukeland Hospital, Bergen, Norway.
Approximately 15% of patients with myasthenia gravis (MG) have thymus neoplasia. These MG with thymoma (MGT) patients show autoantibodies to striated muscle as well as autoantibodies to acetylcholine receptor. To characterize these thymoma-associated muscle antigens, we cloned a number of immunopositive cDNAs by immunoscreening muscle cDNA libraries with sera from MGT patients. Analysis of the isolated cDNAs show that all share a common sequence encoding a distinct region of the titin gene. We expressed this main immunogenic region (MIR) of titin in Escherichia coli, and determined autoantibody serum titers directed against the obtained recombinant antigen in a variety of patients. We could detect titin MIR autoantibodies in 97% of sera from MGT patients but not in control sera from healthy blood donors. Therefore, expressed titin from the MIR of the molecule is a sensitive marker antigen for evaluating the presence of thymoma in MG.
Address correspondence and reprint requests to Dr. J.A. Aarli, Department of Neurology, University of Bergen, 5021 Haukeland Hospital, Bergen, Norway.
Supported by the EC (Z.H., S.S., and K.L.), the Deutsche Forschungsgemeinschaft (S.L.), the Norwegian Cancer Society (A.M.), and Prof. H. Schmidt Gayk (M.G.).
Received August 10, 1992. Accepted for publication in final form December 15, 1992.
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