Titin antibodies in myasthenia gravis: identification of a major immunogenic region of titin.
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.
Gautel
M
M
European Molecular Biology Laboratory, Heidelberg, Germany.
Lakey
A
A
Barlow
D P
DP
Holmes
Z
Z
Scales
S
S
Leonard
K
K
Labeit
S
S
Mygland
A
A
Gilhus
N E
NE
Aarli
J A
JA
D000595:Amino Acid Sequence; D000906:Antibodies / Q000032:analysis*; D064211:Connectin; D004247:DNA / Q000235:genetics; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics / Q000276:immunology*; D009157:Myasthenia Gravis / Q000150:complications / Q000235:genetics / Q000276:immunology*; D011494:Protein Kinases; D013945:Thymoma / Q000276:immunology*; D013950:Thymus Gland / Q000473:pathology; D013953:Thymus Neoplasms / Q000150:complications / Q000276:immunology*
D000906:Antibodies; D064211:Connectin; D009124:Muscle Proteins; C577285:TTN protein, human; D004247:DNA; D011494:Protein Kinases