Cloning and characterization of a Lambert-Eaton myasthenic syndrome antigen.
Lambert-Eaton myasthenic syndrome is a paraneoplastic neuromuscular disorder in which an immune response directed against a small-cell lung tumor crossreacts with antigens in the neuromuscular junction. To isolate and characterize the antigens, we screened a human fetal brain expression library with a high-titer serum from a patient with Lambert-Eaton myasthenic syndrome. This screening resulted in the isolation of a complementary DNA clone encoding an antigen we call myasthenic syndrome antigen B (MysB). Approximately 43% (3 of 7) of Lambert-Eaton myasthenic syndrome sera specifically recognized MysB fusion protein, whereas none of 34 control sera did. The predicted amino acid sequence of this clone shows a high degree of homology to the beta subunit of calcium channel complexes. The MysB pre-messenger RNA is alternatively spliced to yield 3 forms of the protein differing in the domain between two highly conserved alpha-helical segments.
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
M R
MR
Rosenfeld
E
E
Wong
J
J
Dalmau
G
G
Manley
J B
JB
Posner
E
E
Sher
H M
HM
Furneaux
D000941:Antigens / Q000235:genetics* / Q000276:immunology*; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D006801:Humans; D015624:Lambert-Eaton Myasthenic Syndrome / Q000276:immunology*; D015335:Molecular Probes; D008969:Molecular Sequence Data; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism
D000941:Antigens; D015335:Molecular Probes; D012333:RNA, Messenger; D004247:DNA