筋炎関連抗体と間質性肺疾患
多発性筋炎/皮膚筋炎（PM/DM）などの炎症性筋疾患は間質性肺疾患（ILD）を合併することが多く，一言にILDといってもその病型はさまざまであり，治療方針や予後に大きく関連する．また近年，筋炎関連自己抗体の種類により臨床経過が異なることが分かってきた．抗ARS抗体はアミノアシルtRNA合成酵素に対する自己抗体であり，筋炎，発熱，多関節炎，間質性肺炎，Raynaud現象，機械工の手といった抗ARS抗体症候群と呼ばれる臨床症状を呈する．HRCT所見・病理所見としては，非特異性間質性肺炎パターンが多いが，一部に浸潤影を合併するものもある．現在，抗ARS抗体は8種類同定されており，その種類により表現型...
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| Published in | 昭和学士会雑誌 Vol. 83; no. 3; pp. 190 - 197 |
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| Main Authors | , |
| Format | Journal Article |
| Language | Japanese |
| Published |
昭和大学学士会
2023
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| Subjects | |
| Online Access | Get full text |
| ISSN | 2187-719X 2188-529X |
| DOI | 10.14930/jshowaunivsoc.83.190 |
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| Abstract | 多発性筋炎/皮膚筋炎（PM/DM）などの炎症性筋疾患は間質性肺疾患（ILD）を合併することが多く，一言にILDといってもその病型はさまざまであり，治療方針や予後に大きく関連する．また近年，筋炎関連自己抗体の種類により臨床経過が異なることが分かってきた．抗ARS抗体はアミノアシルtRNA合成酵素に対する自己抗体であり，筋炎，発熱，多関節炎，間質性肺炎，Raynaud現象，機械工の手といった抗ARS抗体症候群と呼ばれる臨床症状を呈する．HRCT所見・病理所見としては，非特異性間質性肺炎パターンが多いが，一部に浸潤影を合併するものもある．現在，抗ARS抗体は8種類同定されており，その種類により表現型が異なることが分かってきた．抗MDA5抗体はMDA5と呼ばれる感染防御に関与している蛋白を対応抗原とする自己抗体であり，本抗体陽性例では，筋症状は乏しいが，画像上，びまん性肺胞傷害パターンをとる数日から数週間の経過で呼吸不全に至る急速進行性ILDを高頻度に合併する．2020年にPM/DMに合併するILDに関して，日本呼吸器学会と日本リウマチ学会の共同で作成された「膠原病に伴う間質性肺疾患の診断・治療指針」において，治療アルゴリズム（案）が提案された．特に抗MDA5抗体陽性例では，ステロイドパルス療法を含む高用量PSLに，カルシニューリン阻害薬，シクロホスファミド間欠大量静注療法を初期より用いる3剤併用療法が推奨された．近年，これら3剤併用療法でも効果不十分の症例には血漿交換療法など新たな治療法も行われるようになってきた． |
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| AbstractList | 多発性筋炎/皮膚筋炎（PM/DM）などの炎症性筋疾患は間質性肺疾患（ILD）を合併することが多く，一言にILDといってもその病型はさまざまであり，治療方針や予後に大きく関連する．また近年，筋炎関連自己抗体の種類により臨床経過が異なることが分かってきた．抗ARS抗体はアミノアシルtRNA合成酵素に対する自己抗体であり，筋炎，発熱，多関節炎，間質性肺炎，Raynaud現象，機械工の手といった抗ARS抗体症候群と呼ばれる臨床症状を呈する．HRCT所見・病理所見としては，非特異性間質性肺炎パターンが多いが，一部に浸潤影を合併するものもある．現在，抗ARS抗体は8種類同定されており，その種類により表現型が異なることが分かってきた．抗MDA5抗体はMDA5と呼ばれる感染防御に関与している蛋白を対応抗原とする自己抗体であり，本抗体陽性例では，筋症状は乏しいが，画像上，びまん性肺胞傷害パターンをとる数日から数週間の経過で呼吸不全に至る急速進行性ILDを高頻度に合併する．2020年にPM/DMに合併するILDに関して，日本呼吸器学会と日本リウマチ学会の共同で作成された「膠原病に伴う間質性肺疾患の診断・治療指針」において，治療アルゴリズム（案）が提案された．特に抗MDA5抗体陽性例では，ステロイドパルス療法を含む高用量PSLに，カルシニューリン阻害薬，シクロホスファミド間欠大量静注療法を初期より用いる3剤併用療法が推奨された．近年，これら3剤併用療法でも効果不十分の症例には血漿交換療法など新たな治療法も行われるようになってきた． |
| Author | 西見, 慎一郎 若林, 邦伸 |
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| References | 17） Targoff IN. Myositis specific autoantibodies. Curr Rheumatol Rep. 2006;8:196-203. 23） Tsuji H, Nakashima R, Hosono Y, et al. Multicenter prospective study of the efficacy and safety of combined immunosuppressive therapy with high-dose glucocorticoid, tacrolimus, and cyclophosphamide in interstitial lung diseases accompanied by anti-melanoma differentiation-associated gene 5-positive dermatomyositis. Arthritis Rheumatol. 2020;72:488-498. 22） Yamasaki Y, Yamada H, Yamasaki M, et al. Intravenous cyclophosphamide therapy for progressive interstitial pneumonia in patients with polymyositis/dermatomyositis. Rheumatology （Oxford）. 2007;46:124-130. 18） 日本呼吸器学会・日本リウマチ学会合同膠原病に伴う間質性肺疾患診断・治療指針2020作成委員会編．実臨床における治療選択．膠原病に伴う間質性肺疾患診断・治療指針．第1版．東京: 株式会社メディカルレビュー社; 2020. p79 21） Wilkes MR, Sereika SM, Fertig N, et al. Treatment of antisynthetase-associated interstitial lung disease with tacrolimus. Arthritis Rheum. 2005;52:2439-2446. 26） Kurasawa K, Arai S, Namiki Y, et al. Tofacitinib for refractory interstitial lung diseases in anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis. Rheumatology （Oxford）. 2018;57:2114-2119. 1） Fujisawa T, Hozumi H, Kono M, et al. Prognostic factors for myositis-associated interstitial lung disease. PLoS One. 2014;9:e98824.（accessed 2022 Nov 13） https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048238/pdf/pone.0098824.pdf 11） Chino H, Sekine A, Baba T, et al. Interstitial lung disease with anti-melanoma differentiation-associated protein 5 antibody: Rapidly Progressive Perilobular Opacity. Intern Med. 2019;58:2605-2613. 6） Waseda Y, Johkoh T, Egashira R, et al. Antisynthetase syndrome: pulmonary computed tomography findings of adult patients with antibodies to aminoacyl-tRNA synthetases. Eur J Radiol. 2016;85:1421-1426. 13） Gono T, Sato S, Kawaguchi Y, et al. Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Rheumatology （Oxford）. 2012;51:1563-1570. 14） Sato S, Masui K, Nishina N, et al. Initial predictors of poor survival in myositis-associated interstitial lung disease: a multicentre cohort of 497 patients. Rheumatology （Oxford）. 2018;57:1212-1221. 3） Nakashima R, Imura Y, Hosono Y, et al. The multicenter study of a new assay for simultaneous detection of multiple anti-aminoacyl-tRNA synthetases in myositis and interstitial pneumonia. PLoS One. 2014;9:e85062.（accessed 2022 Nov 13） https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891809/pdf/pone.0085062.pdf 8） Kurtzman DJB, Vleugels RA. Anti-melanoma differentiation-associated gene 5 （MDA5） dermatomyositis: a concise review with an emphasis on distinctive clinical features. J Am Acad Dermatol. 2018;78:776-785. 25） Saito T, Mizobuchi M, Miwa Y, et al. Anti-MDA-5 antibody-positive clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease treated with therapeutic plasma exchange: a case series. J Clin Apher. 2021;36:196-205. 12） Gono T. Kawaguchi Y, Satoh T, et al. Clinical manifestation and prognostic factor in anti-melanoma differentiation-associated gene 5 antibody-associated interstitial lung disease as a complication of dermatomyositis. Rheumatology （Oxford）. 2010;49:1713-1719. 2） Yoshifuji H. Biomarkers and autoantibodies of interstitial lung disease with idiopathic inflammatory myopathies. Clin Med Insights Circ Respir Pulm Med. 2016;9（Suppl 1）:141-146. 7） Sato S, Hirakata M, Kuwana M, et al. Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis. Arthritis Rheum. 2005;52:1571-1576. 10） Tanizawa K, Hanada T, Nakashima R, et al. HRCT features of interstitial lung disease in dermatomyositis with anti-CADM-140 antibody. Respir Med. 2011;105:1380-1387. 16） Targoff IN. Reichlin M. The association between Mi-2 antibodies and dermatomyositis. Arthritis Rheum. 1985;28:796-803. 20） Yamakawa H, Hagiwara E, Kitamura H, et al. Predictive factors for the long-term deterioration of pulmonary function in interstitial lung disease associated with anti-aminoacyl-tRNA synthetase antibodies. Respiration. 2018;96:210-221. 5） Marie I, Josse S, Decaux O, et al. Comparison of long-term outcome between anti-Jo1- and anti-PL7/PL12 positive patients with antisynthetase syndrome. Autoimmun Rev. 2012;11:739-745. 15） Gono T, Kawaguchi Y, Ozeki E, et al. Serum ferritin correlates with activity of anti-MDA5 antibody-associated acute interstitial lung disease as a complication of dermatomyositis. Mod Rheumatol. 2011;21:223-227. 19） Takato H, Waseda Y, Watanabe S, et al. Pulmonary manifestations of anti-ARS antibody positive interstitial pneumonia--with or without PM/DM. Respir Med. 2013;107:128-133. 9） Sato S, Hoshino K, Satoh T, et al. RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: association with rapidly progressive interstitial lung disease. Arthritis Rheum. 2009;60:2193-2200. 4） Tanizawa K, Hanada T, Nakashima R, et al. The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies. Respir Med. 2017;127:57-64. 24） Shirakashi M, Nakashima R, Tsuji H, et al. Efficacy of plasma exchange in anti-MDA5-positive dermatomyositis with interstitial lung disease under combined immunosuppressive treatment. Rheumatology （Oxford）. 2020;59:3284-3292. |
| References_xml | – reference: 14） Sato S, Masui K, Nishina N, et al. Initial predictors of poor survival in myositis-associated interstitial lung disease: a multicentre cohort of 497 patients. Rheumatology （Oxford）. 2018;57:1212-1221. – reference: 2） Yoshifuji H. Biomarkers and autoantibodies of interstitial lung disease with idiopathic inflammatory myopathies. Clin Med Insights Circ Respir Pulm Med. 2016;9（Suppl 1）:141-146. – reference: 23） Tsuji H, Nakashima R, Hosono Y, et al. Multicenter prospective study of the efficacy and safety of combined immunosuppressive therapy with high-dose glucocorticoid, tacrolimus, and cyclophosphamide in interstitial lung diseases accompanied by anti-melanoma differentiation-associated gene 5-positive dermatomyositis. Arthritis Rheumatol. 2020;72:488-498. – reference: 26） Kurasawa K, Arai S, Namiki Y, et al. Tofacitinib for refractory interstitial lung diseases in anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis. Rheumatology （Oxford）. 2018;57:2114-2119. – reference: 18） 日本呼吸器学会・日本リウマチ学会合同膠原病に伴う間質性肺疾患診断・治療指針2020作成委員会編．実臨床における治療選択．膠原病に伴う間質性肺疾患診断・治療指針．第1版．東京: 株式会社メディカルレビュー社; 2020. p79． – reference: 13） Gono T, Sato S, Kawaguchi Y, et al. Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Rheumatology （Oxford）. 2012;51:1563-1570. – reference: 12） Gono T. Kawaguchi Y, Satoh T, et al. Clinical manifestation and prognostic factor in anti-melanoma differentiation-associated gene 5 antibody-associated interstitial lung disease as a complication of dermatomyositis. Rheumatology （Oxford）. 2010;49:1713-1719. – reference: 7） Sato S, Hirakata M, Kuwana M, et al. Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis. Arthritis Rheum. 2005;52:1571-1576. – reference: 3） Nakashima R, Imura Y, Hosono Y, et al. The multicenter study of a new assay for simultaneous detection of multiple anti-aminoacyl-tRNA synthetases in myositis and interstitial pneumonia. PLoS One. 2014;9:e85062.（accessed 2022 Nov 13） https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891809/pdf/pone.0085062.pdf – reference: 19） Takato H, Waseda Y, Watanabe S, et al. Pulmonary manifestations of anti-ARS antibody positive interstitial pneumonia--with or without PM/DM. Respir Med. 2013;107:128-133. – reference: 24） Shirakashi M, Nakashima R, Tsuji H, et al. Efficacy of plasma exchange in anti-MDA5-positive dermatomyositis with interstitial lung disease under combined immunosuppressive treatment. Rheumatology （Oxford）. 2020;59:3284-3292. – reference: 6） Waseda Y, Johkoh T, Egashira R, et al. Antisynthetase syndrome: pulmonary computed tomography findings of adult patients with antibodies to aminoacyl-tRNA synthetases. Eur J Radiol. 2016;85:1421-1426. – reference: 20） Yamakawa H, Hagiwara E, Kitamura H, et al. Predictive factors for the long-term deterioration of pulmonary function in interstitial lung disease associated with anti-aminoacyl-tRNA synthetase antibodies. Respiration. 2018;96:210-221. – reference: 10） Tanizawa K, Hanada T, Nakashima R, et al. HRCT features of interstitial lung disease in dermatomyositis with anti-CADM-140 antibody. Respir Med. 2011;105:1380-1387. – reference: 15） Gono T, Kawaguchi Y, Ozeki E, et al. Serum ferritin correlates with activity of anti-MDA5 antibody-associated acute interstitial lung disease as a complication of dermatomyositis. Mod Rheumatol. 2011;21:223-227. – reference: 5） Marie I, Josse S, Decaux O, et al. Comparison of long-term outcome between anti-Jo1- and anti-PL7/PL12 positive patients with antisynthetase syndrome. Autoimmun Rev. 2012;11:739-745. – reference: 17） Targoff IN. Myositis specific autoantibodies. Curr Rheumatol Rep. 2006;8:196-203. – reference: 21） Wilkes MR, Sereika SM, Fertig N, et al. Treatment of antisynthetase-associated interstitial lung disease with tacrolimus. Arthritis Rheum. 2005;52:2439-2446. – reference: 1） Fujisawa T, Hozumi H, Kono M, et al. Prognostic factors for myositis-associated interstitial lung disease. PLoS One. 2014;9:e98824.（accessed 2022 Nov 13） https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048238/pdf/pone.0098824.pdf – reference: 4） Tanizawa K, Hanada T, Nakashima R, et al. The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies. Respir Med. 2017;127:57-64. – reference: 8） Kurtzman DJB, Vleugels RA. Anti-melanoma differentiation-associated gene 5 （MDA5） dermatomyositis: a concise review with an emphasis on distinctive clinical features. J Am Acad Dermatol. 2018;78:776-785. – reference: 9） Sato S, Hoshino K, Satoh T, et al. RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: association with rapidly progressive interstitial lung disease. Arthritis Rheum. 2009;60:2193-2200. – reference: 11） Chino H, Sekine A, Baba T, et al. Interstitial lung disease with anti-melanoma differentiation-associated protein 5 antibody: Rapidly Progressive Perilobular Opacity. Intern Med. 2019;58:2605-2613. – reference: 25） Saito T, Mizobuchi M, Miwa Y, et al. Anti-MDA-5 antibody-positive clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease treated with therapeutic plasma exchange: a case series. J Clin Apher. 2021;36:196-205. – reference: 16） Targoff IN. Reichlin M. The association between Mi-2 antibodies and dermatomyositis. Arthritis Rheum. 1985;28:796-803. – reference: 22） Yamasaki Y, Yamada H, Yamasaki M, et al. Intravenous cyclophosphamide therapy for progressive interstitial pneumonia in patients with polymyositis/dermatomyositis. Rheumatology （Oxford）. 2007;46:124-130. |
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| Snippet | 多発性筋炎/皮膚筋炎（PM/DM）などの炎症性筋疾患は間質性肺疾患（ILD）を合併することが多く，一言にILDといってもその病型はさまざまであり，治療方針や予後に大きく関... |
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| Title | 筋炎関連抗体と間質性肺疾患 |
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