抗MDA5抗体陽性皮膚筋炎/急速進行性間質性肺炎の病態解明および新規治療法の開発

抗MDA5抗体阳性皮肌炎/急进性间质性肺炎病理学的阐明及新疗法的开发

• 批准号: 21K08481
• 负责人: 佐藤 慎二
• 金额: $ 2.75万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K08481/
• 关键词: 抗MDA5抗体; 皮膚筋炎; 間質性肺疾患; 再発; 急速進行性間質性肺疾患; 縦隔気腫; 予後不良因子; 免疫学; 無筋症性皮膚筋炎; 急速進行性間質性肺炎

【目的】抗melanoma differentiation-associated gene 5 (MDA5)抗体陽性の皮膚筋炎(DM)に併発した急速進行性間質性肺炎(RP-ILD)の寛解後の再発に関する検討．【方法】2020年まで当科を受診したRP-ILD併発抗MDA5抗体陽性DM患者41例のうち，寛解を達成した28症例を対象にした．入院時の年齢, 性別, 入院時の酸素投与量, 血清クレアチニンキナーゼ(CK), KL-6, CRP, フェリチン, 抗MDA5抗体の抗体価, 胸部HRCT画像所見を寛解維持群，再発群に層別化して後ろ向きに比較検討した．経過中に何らかの臨床症状の悪化を認め，免疫抑制療法が強化された症例を再発例と定義した．【結果】41例中，13例が治療に十分反応せず，急性期に呼吸不全により死亡した．治療が奏功し寛解を達成した28例のうち5例(18%)が維持療法中に再発した．再発例は，男性2名、女性3名,平均年齢50±11歳で4症例がCADMであった．再発時点で，2例で発熱を認めたが，呼吸困難を自覚したのは1例のみであった．血清CK，CRPおよびフェリチン値は正常範囲より上昇した症例は1例のみであったが，血清KL-6値は3例で正常範囲より上昇した．再発前後で測定可能であった3例全例の抗MDA5抗体力価はcut-off以上に再上昇を認めたが，寛解維持群では抗体価の再上昇は認めなかった(60% vs. 0%，P=0.003)．再発群の全5例でコルチコステロイドの増量，4例でシクロスポリンAの増量/追加,シクロフォスファミドの追加およびJAK阻害薬が開始されて，全例で呼吸器症状などの臨床症状の改善を認めた．【結論】抗MDA5抗体陽性DMに併発するILDの再発は稀とされているが，再発例も存在し，その再発予測には抗MDA5抗体力価の推移が有用であることが示唆された．

Objective To investigate the relationship between the development of dermatodynia (DM) with anti-melanoma differentiation-associated gene 5 (MDA5) antibody positive and rapid progressive interstitial pneumonia (RP-ILD) and its recurrence after remission. [Methods] In 2020, 41 cases of RP-ILD and anti-MDA 5 antibody positive DM patients were diagnosed in the department, and 28 cases of RP-ILD were diagnosed in the department. Age at admission, gender, acid dose at admission, serum CK, KL-6, CRP, anti-MDA 5 antibody, HRCT findings, maintenance group, re-stratification group, post-treatment group, comparison group. In the middle of the disease, the clinical symptoms were identified, and immunosuppressive therapy was intensified. [Results] Among the 41 cases, 13 cases died of respiratory failure in acute stage. 28 cases were successful in treatment and 5 cases (18%) were successful in maintenance therapy. There were 2 males and 3 females with an average age of 50±11 years. 2 cases of fever, 1 case of dyspnea, 2 cases of fever, 1 case of dyspnea. Serum CK, CRP and KL-6 levels increased from normal in 1 case to normal in 3 cases. 3 cases of anti-MDA 5 antibody strength increased from cut-off to re-recognition (60% vs. 0%, P=0.003). All 5 cases of the re-development group showed an increase in the amount of respiratory symptoms, 4 cases showed an increase in the amount of respiratory symptoms, 4 cases showed an increase/addition of respiratory symptoms, 4 cases showed an increase in the amount of respiratory symptoms, 4 cases showed an increase/addition of respiratory symptoms, 4 cases showed an increase in the amount of respiratory symptoms, 4 cases showed an increase in the amount of respiratory symptoms, 4 cases showed an increase/addition of respiratory symptoms, 4 cases showed an increase in the amount of respiratory symptoms, 4 cases showed an increase in the amount of respiratory symptoms, 4 cases showed an increase/addition of respiratory symptoms, 4 cases showed an increase in the amount of respiratory symptoms, 4 cases showed an increase/addition of respiratory symptoms, 4 cases showed an increase/addition of respiratory symptoms, and 4 cases showed an increase/addition of respiratory symptoms. [Conclusion] Anti-MDA-5 antibody positive DM and ILD recurrence is rare, recurrence exists, and the progression of anti-MDA-5 antibody activity is useful in predicting ILD recurrence.

项目成果

特発性炎症性筋疾患に見出される自己抗体

特发性炎症性肌病中发现自身抗体

• 发表时间: 2021
• 作者: Honda Fumika;Tsuboi Hiroto;Ono Yuko;Abe Saori;Takahashi Hiroyuki;Ito Kiyoaki;Yamada Kazunori;Kawano Mitsuhiro;Kondo Yuya;Asano Kenichi;Tanaka Masato;Malissen Marie;Malissen Bernard;Matsumoto Isao;Sumida Takayuki;佐藤慎二
• 通讯作者: 佐藤慎二

炎症性筋疾患関連間質性肺疾患に縦隔気腫を合併した23例の臨床的検討

炎症性肌病相关间质性肺疾病并发纵隔积气23例临床研究

• 发表时间: 2021
• 作者: 平野 一貴;小島 梓;志村 佳瑚;石井 晶;杉山 麻衣;中込 陽子; 泉 勇人;倉林 賢慶;佐々木 則子;細野 祐司;山田 千穂;佐藤 慎二
• 通讯作者: 佐藤 慎二

Association of Pneumomediastinum with Poor Prognosis in Patients with Myositis-Associated Interstitial Lung Disease.

纵隔气肿与肌炎相关间质性肺病患者预后不良的关系。

• 发表时间: 2021
• 作者: Hirano K;Kojima A;Ishii A;Sugiyama M;Izumi Y;Sasaki N;Hosono Y;Yamada C;Sato S.
• 通讯作者: Sato S.

多発性筋炎／皮膚筋炎の診断・治療の最前線

多发性肌炎/皮肌炎诊治前沿

• 发表时间: 2021
• 作者: Koyama Teidai;Miura Kento;Yamasaki Norimasa;Ogata Sawako;Ito Daiki;Saeki Mayumi;Hiroi Takachika;Mori Akio;Kaminuma Osamu;佐藤慎二
• 通讯作者: 佐藤慎二