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

Abstract

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 substrate. Using immunoprecipitation and Western blotting, we then examined whether anti‐155/140–positive sera recognized transcription intermediary factor 1α (TIF‐1α), TIF‐1β, and TIF‐1γ. The clinical associations of antigen reactivity were also evaluated. Results: Anti‐155/140–positive sera reacted with 140‐kd TIF‐1α in addition to 155‐kd TIF‐1γ. Among sera from 456 DM patients, 52 were reactive with both TIF‐1α and TIF‐1γ, while another 25 were reactive with TIF‐1γ alone. Additionally, 7 were reactive with TIF‐1β. Malignancy was more frequently found in adult patients with both anti–TIF‐1α and anti–TIF‐1γ antibodies than in those with anti–TIF‐1γ 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‐1α and TIF‐1β, in addition to TIF‐1γ. Since TIF‐1 proteins have significant roles in oncogenesis, these antibodies may be produced during misdirected antitumor immunity.