Myositis-specific anti-155/140 autoantibodies target transcription intermediary factor 1 family proteins

Objective To identify the 140-kd autoantigen recognized by anti-155/140 autoantibodies that are associated with adult cancer-associated dermatomyositis (DM) and juvenile DM and to determine the clinical relevance of anti-155/140 antibodies in a large cohort. Methods. Sera from 456 DM patients were assessed for the presence of anti-155/140 antibodies by immunoprecipitation using K562 cell extracts as sub-strate. Using immunoprecipitation and Western blotting, we then examined whether anti-155/140-positive sera recognized transcription intermediary factor 1 alpha (TIF-1 alpha), TIF-1 alpha, and TIF-1 alpha. The clinical associations of antigen reactivity were also evaluated. Results. Anti-155/140-positive sera reacted with 140-kd TIF-1 alpha in addition to 155-kd TIF-1 alpha. Among sera from 456 DM patients, 52 were reactive with both TIF-1 alpha and TIF-1 alpha, while another 25 were reactive with TIF-1 alpha alone. Additionally, 7 were reactive with TIF-1 alpha. Malignancy was more frequently found in adult patients with both anti-TIF-1 alpha and anti-TIF-1 alpha antibodies than in those with anti-TIF-1 alpha antibodies alone (73% versus 50%; P < 0.05). In addition to juvenile DM patients and middle-aged and older DM patients with high percentages of malignancy, 8 young adult DM patients without malignancy had these autoantibodies. Conclusion. Anti-155/140 antibodies target TIF-1 family proteins, TIF-1 alpha and TIF-1 alpha, in addition to TIF-1 alpha. Since TIF-1 proteins have significant roles in oncogenesis, these antibodies may be produced during misdirected antitumor immunity.