Fujimoto Manabu, Hamaguchi Yasuhito, Kaji Kenzo, Matsushita Takashi, Ichimura Yuki, Kodera Masanari, Ishiguro Naoko, Ueda-Hayakawa Ikuko, Asano Yoshihide, Ogawa Fumihide, Fujikawa Keita, Miyagi Takuya, Mabuchi Eriko, Hirose Kenji, Akimoto Narihiro, Hatta Naohito, Tsutsui Kiyohiro, Higashi Akira, Igarashi Atsuyuki, Seishima Mariko, Hasegawa Minoru, Takehara Kazuhiko
Department of Dermatology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan.
Arthritis Rheum. 2012 Feb;64(2):513-22. doi: 10.1002/art.33403.
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.
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.
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.
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.
鉴定与成人癌症相关性皮肌炎（DM）及青少年DM相关的抗155/140自身抗体所识别的140-kd自身抗原，并在一个大型队列中确定抗155/140抗体的临床相关性。
以K562细胞提取物为底物，通过免疫沉淀法检测456例DM患者血清中抗155/140抗体的存在情况。然后利用免疫沉淀和蛋白质印迹法，检测抗155/140阳性血清是否识别转录中介因子1α（TIF-1α）、TIF-1β和TIF-1γ。还评估了抗原反应性的临床关联。
抗155/140阳性血清除了与155-kd的TIF-1γ反应外，还与140-kd的TIF-1α反应。在456例DM患者的血清中，52例同时与TIF-1α和TIF-1γ反应，另外25例仅与TIF-1γ反应。此外，7例与TIF-1β反应。与仅具有抗TIF-1γ抗体的成人患者相比，同时具有抗TIF-1α和抗TIF-1γ抗体的成人患者中恶性肿瘤更为常见（73%对50%；P<0.05）。除了青少年DM患者以及恶性肿瘤比例较高的中老年DM患者外，8例无恶性肿瘤的“青年成人”DM患者也有这些自身抗体。
抗155/140抗体除了靶向TIF-1γ外，还靶向TIF-1家族蛋白TIF-1α和TIF-1β。由于TIF-1蛋白在肿瘤发生中具有重要作用，这些抗体可能在错误导向的抗肿瘤免疫过程中产生。
