Clinical and pathophysiological significance of novel identified anti-IFIH1/MDA5 autoantibody in amyopathic dermatomyositis

新型抗 IFIH1/MDA5 自身抗体在无肌病性皮肌炎中的临床和病理生理学意义

• 批准号: 22659185
• 负责人: MIMORI Tsuneyo
• 金额: $ 2.07万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22659185/
• 关键词: IFIH1; MDA5; CADM-140; 自己抗体; 皮膚筋炎; 間質性肺炎; サイトカイン; HLA; ADM

A disease-specific autoantibody, termed anti-CADM-140 antibody, is found in patients with amyopathic dermatomyositis accompanied with lethal acute interstitial pneumonia. We identified that the target autoantigen recognized by anti-CADM-140 antibody was IFIH1/MDA5, a viral RNA receptor in cytoplasm. The patients with anti-CADM-140 antibody revealed higher level of serum ferritin as well as IL-6, IL-10, IL-18 and M-CSF than antibody-negative dermatomyositis patients, suggesting the macrophage activating state. The intensive immunosuppressive therapy(high-dose glucocorticoids, cyclosporine and intravenous cyclophosphamide pulse) appeared to improve a life prognosis of antibody-positive patients when compared with the conventional step-up therapy.

在患有致命的急性急性间质性肺炎的患者中发现了一种疾病特异性的自身抗体，称为抗CADM-140抗体。我们发现，抗CADM-140抗体识别的靶自身抗原是IFIH1/MDA5，这是细胞质中的病毒RNA受体。抗CADM-140抗体的患者比抗体阴性皮肤瘤患者更高的血清铁蛋白以及IL-6，IL-10，IL-18和M-CSF水平更高，这表明巨噬细胞激活了巨噬细胞。与常规的升级治疗相比，强化的免疫抑制治疗（高剂量糖皮质激素，环孢菌素和静脉注射环磷酰胺脉冲）似乎改善了抗体阳性患者的寿命预后。

项目成果

自己抗体抗アミノアシルtRNA合成酵素抗体を検出するための新規ELISAの開発

开发新的 ELISA 检测自身抗体抗氨酰基-tRNA 合成酶抗体

• 发表时间: 2011
• 作者: 中嶋蘭;井村嘉孝;瀬戸美苗;村上昭弘;小林志緒;細野祐司;湯川尚一郎;吉藤元;川端大介;大村浩一郎;臼井崇;藤井隆夫;三森経世
• 通讯作者: 三森経世

Detection of antisynthetase syndrome in patients with idiopathic interstitial pneumonias

• DOI: 10.1016/j.rmed.2011.03.022
• 发表时间: 2011-08-01
• 期刊: RESPIRATORY MEDICINE
• 影响因子: 4.3
• 作者: Watanabe, Kizuku;Handa, Tomohiro;Mishima, Michiaki
• 通讯作者: Mishima, Michiaki

A New ELISA System for Detecting Autoantibodies to aminoacyl-tRNA Synthetases : Usefulness in Myositis and Interstitial Pneumonia.

用于检测氨酰-tRNA 合成酶自身抗体的新型 ELISA 系统：在肌炎和间质性肺炎中的有用性。

• 发表时间: 2010
• 作者: Ran Nakashima;Yoshitaka Imura;Shio Kobayashi;Yuji Hosono;Naoichiro Yukawa;Daisuke Kawabata;Takaki Nojima;Koichiro Ohmura;Takashi Usui;Takao Fujii;Minae Seto;Akihiro Murakami;Tsuneyo Mimori
• 通讯作者: Tsuneyo Mimori

HRCT features of interstitial lung disease in dermatomyositis with anti-CADM-140 antibody

• DOI: 10.1016/j.rmed.2011.05.006
• 发表时间: 2011-09-01
• 期刊: RESPIRATORY MEDICINE
• 影响因子: 4.3
• 作者: Tanizawa, Kiminobu;Handa, Tomohiro;Mishima, Michiaki
• 通讯作者: Mishima, Michiaki

Clinical and Pathogenic Significance of Autoantibodies in Autoimmune Myositis and Interstitial Lung Disease

自身抗体在自身免疫性肌炎和间质性肺疾病中的临床和致病意义

• 发表时间: 2011
• 作者: Takahashi K;Oka A;Mizuguchi M;Saitoh M;Takita J;Sato A;Mimaki M;Kato M;Ogawa S;Igarashi T;松井啓隆;Mimori T
• 通讯作者: Mimori T