抗MDA5抗体相关皮肌炎
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摘要
抗黑色素瘤分化相关基因5 (melanoma differentiation associated gene 5, MDA5)抗体是特发性炎性肌病(idiopathic inflammatory myopathy, IIM)中临床无肌病皮肌炎(clinical amyopathic dermatomyositis, CADM)亚型相对常见的肌炎特异性抗体(myositis specific antibody, MSA),在亚裔人群与快速进展性肺间质病变(rapidly progressive interstitial lung disease, RPILD)高度相关,患者病情往往较重,对常规免疫治疗效果不佳,预后极差,近年受到临床医师的广泛关注。目前,本病发病机制尚不明确,治疗上无统一标准,本文综述抗MDA5抗体相关皮肌炎(dermatomyositis, DM)基础研究及临床研究的相关进展。
Melanoma differentiation-associated gene 5(MDA5) antibody is the relatively most common myositis specificity antibody(MSA) in clinically amyopathic dermatomyositis(CADM),the subtype of idiopathic inflammatory myopathy(IIM), which is highly correlated with rapidly progressive interstitial lung disease(RPILD) in the Asian population. Generally speaking, the disease is always severe, with poor effect of conventional immunosuppression therapies and poor prognoses, which has attracted considerable attention from clinicians in recent years. At present, the pathogenesis of this disease is not clear, and there is no unified standard for the treatment. This review summarized recent development of anti-MDA5 antibody-positive dermatomyositis(DM) in the field of both basic research and clinical research.
Melanoma differentiation-associated gene 5(MDA5) antibody is the relatively most common myositis specificity antibody(MSA) in clinically amyopathic dermatomyositis(CADM),the subtype of idiopathic inflammatory myopathy(IIM), which is highly correlated with rapidly progressive interstitial lung disease(RPILD) in the Asian population. Generally speaking, the disease is always severe, with poor effect of conventional immunosuppression therapies and poor prognoses, which has attracted considerable attention from clinicians in recent years. At present, the pathogenesis of this disease is not clear, and there is no unified standard for the treatment. This review summarized recent development of anti-MDA5 antibody-positive dermatomyositis(DM) in the field of both basic research and clinical research.
引文
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[3] Baechler EC,Bilgic H,Reed AM.Type I interferon pathway in adult and juvenile dermatomyositis [J].Arthritis Res Ther,2011,13:249.
[4] Ekholm L,Kahlenberg JM,Barbasso Helmers S,et al.Dysfunction of endothelial progenitor cells is associated with the type I IFN pathway in patients with polymyositis and dermatomyositis [J].Rheumatology (Oxford),2016,55:1987-1992.
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[6] Sadler AJ.The role of MDA5 in the development of autoimmune disease [J].J Leukoc Biol,2018,103:185-192.
[7] Kawasumi H,Katsumata Y,Nishino A,et al.Association of Serum Soluble CD163 with Polymyositis and Dermatomyositis,Especially in Anti-MDA5 Antibody-positive Cases [J].J Rheumatol,2018,45:947-955.
[8] Chen F,Wang D,Shu X,et al.Anti-MDA5 antibody is associated with A/SIP and decreased T cells in peripheral blood and predicts poor prognosis of ILD in Chinese patients with dermatomyositis [J].Rheumatol Int,2012,32:3909-3915.
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[21] Kurasawa K,Arai S,Namiki Y,et al.Tofacitinib for refractory interstitial lung diseases in anti-melanoma differentiation-associa-ted 5 gene antibody-positive dermatomyositis [J].Rheumatology (Oxford),2018,57:2114-2119.
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[26] Ma X,Chen Z,Hu W,et al.Clinical and serological features of patients with dermatomyositis complicated by spontaneous pneumomediastinum [J].Clin Rheumatol,2016,35:489-493.
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[29] Bonnefoy O,Ferretti G,Calaque O,et al.Serial chest CT findings in interstitial lung disease associated with polymyositis-dermatomyositis [J].Eur J Radiol,2004,49:235-244.
[30] Arakawa H,Yamada H,Kurihara Y,et al.Nonspecific interstitial pneumonia associated with polymyositis and dermatomyositis:serial high-resolution CT findings and functional correlation [J].Chest,2003,123:1096-1103.
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[32] Ichikado K,Suga M,Muller NL,et al.Acute interstitial pneumonia:comparison of high-resolution computed tomography findings between survivors and nonsurvivors [J].Am J Respir Crit Care Med,2002,165:1551-1556.
[33] 邹静.临床无肌病型皮肌炎合并急性间质性肺病预后相关危险因素及中性粒细胞、Th17细胞在疾病发病机制中作用的研究[D].In:上海交通大学,2015.
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[35] Chino H,Sekine A,Baba T,et al.Radiological and pathological correlation in anti-MDA5 antibody-positive interstitial lung disease:rapidly progressive perilobular opacities and diffuse alveolar damage[J].Intern Med,2016,55:2241-2246.
[36] Cox NH.Amyopathic dermatomyositis,photosensitivity and hydroxychloroquine[J].Br J Dermatol,1995,132:1016-1017.
[37] Hornung T,Ko A,Tuting T,et al.Efficacy of low-dose methotrexate in the treatment of dermatomyositis skin lesions[J].Clin Exp Dermatol,2012,37:139-142.
[38] Tsujimura S,Saito K,Tanaka Y.Complete resolution of dermatomyositis with refractory cutaneous vasculitis by intravenous cyclophosphamide pulse therapy[J].Intern Med,2008,47:1935-1940.
[39] Dinh HV,McCormack C,Hall S,et al.Rituximab for the treatment of the skin manifestations of dermatomyositis:a report of 3 cases[J].J Am Acad Dermatol,2007,56:148-153.
[40] Flores-Suarez LF,Morales H,Angeles A,et al.Drug-induced amyopathic dermatomyositis[J].J Clin Rheumatol,2002,8:50-54.
[41] Marco Puche A,Calvo Penades I,Lopez Montesinos B.Effectiveness of the treatment with intravenous pamidronate in calcinosis in juvenile dermatomyositis[J].Clin Exp Rheumatol,2010,28:135-140.
[42] 叶霜,黄文群,吴美芳,等.以急进性肺间质病变为突出表现的无肌炎的皮肌炎[J].中华风湿病学杂志,2006,10:527-533.
[43] Kurita T,Yasuda S,Amengual O,et al.The efficacy of calcineurin inhibitors for the treatment of interstitial lung disease associated with polymyositis/dermatomyositis[J].Lupus,2015,24:3-9.
[44] 郭强,照日格图,吴美芳,等.伴急性/亚急性间质性肺炎的临床无肌炎皮肌炎1年生存随访及危险因素分析[J].上海医学,2009,32:860-864,封862.
[45] Miyazaki E,Ando M,Muramatsu T,et al.Early assessment of rapidly progressive interstitial pneumonia associated with amyopathic dermatomyositis[J].Clin Rheumatol,2007,26:436-439.
[46] Ando M,Miyazaki E,Yamasue M,et al.Successful treatment with tacrolimus of progressive interstitial pneumonia associated with amyopathic dermatomyositis refractory to cyclosporine[J].Clin Rheumatol,2010,29:443-445.
[47] Yamasaki Y,Yamada H,Yamasaki M,et al.Intravenous cyclophosphamide therapy for progressive interstitial pneumonia in patients with polymyositis/dermatomyositis[J].Rheumatology (Oxford),2007,46:124-130.
[48] Nawata Y,Kurasawa K,Takabayashi K,et al.Corticosteroid resistant interstitial pneumonitis in dermatomyositis/polymyositis:prediction and treatment with cyclosporine[J].J Rheumatol,1999,26:1527-1533.
[49] Barnes H,Holland AE,Westall GP,et al.Cyclophosphamide for connective tissue disease-associated interstitial lung disease[J].Cochrane Database Syst Rev,2018,1:Cd010908.
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[2] Chen Z,Cao M,Plana MN,et al.Utility of anti-melanoma differentiation-associated gene 5 antibody measurement in identifying patients with dermatomyositis and a high risk for developing rapidly progressive interstitial lung disease:a review of the literature and a meta-analysis [J].Arthritis Care Res (Hoboken),2013,65:1316-1324.
[3] Baechler EC,Bilgic H,Reed AM.Type I interferon pathway in adult and juvenile dermatomyositis [J].Arthritis Res Ther,2011,13:249.
[4] Ekholm L,Kahlenberg JM,Barbasso Helmers S,et al.Dysfunction of endothelial progenitor cells is associated with the type I IFN pathway in patients with polymyositis and dermatomyositis [J].Rheumatology (Oxford),2016,55:1987-1992.
[5] Volc-Platzer B.Dermatomyositis-update [J].Hautarzt,2015,66:604-610.
[6] Sadler AJ.The role of MDA5 in the development of autoimmune disease [J].J Leukoc Biol,2018,103:185-192.
[7] Kawasumi H,Katsumata Y,Nishino A,et al.Association of Serum Soluble CD163 with Polymyositis and Dermatomyositis,Especially in Anti-MDA5 Antibody-positive Cases [J].J Rheumatol,2018,45:947-955.
[8] Chen F,Wang D,Shu X,et al.Anti-MDA5 antibody is associated with A/SIP and decreased T cells in peripheral blood and predicts poor prognosis of ILD in Chinese patients with dermatomyositis [J].Rheumatol Int,2012,32:3909-3915.
[9] Kohlmeier JE,Cookenham T,Roberts AD,et al.Type I interferons regulate cytolytic activity of memory CD8(+) T cells in the lung airways during respiratory virus challenge [J].Immunity,2010,33:96-105.
[10] 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 [J].Rheumatology (Oxford),2012,51:1563-1570.
[11] Wakiguchi H,Hasegawa S,Hirano R,et al.Successful control of juvenile dermatomyositis-associated macrophage activation syndrome and interstitial pneumonia:distinct kinetics of interleukin-6 and -18 levels [J].Pediatr Rheumatol Online J,2015,13:49.
[12] Cobo-Ibanez T,Lopez-Longo FJ,Joven B,et al.Long-term pulmonary outcomes and mortality in idiopathic inflammatory myopathies associated with interstitial lung disease [J].Clin Rheumatol,2019,38:803-815.
[13] Fiorentino D,Chung L,Zwerner J,et al.The mucocutaneous and systemic phenotype of dermatomyositis patients with antibodies to MDA5 (CADM-140):a retrospective study [J].J Am Acad Dermatol,2011,65:25-34.
[14] Ito M,Kaise S,Suzuki S,et al.Clinico-laboratory characteristics of patients with dermatomyositis accompanied by rapidly progressive interstitial lung disease [J].Clin Rheumatol,1999,18:462-467.
[15] Allenbach Y,Leroux G,Suarez-Calvet X,et al.Dermatomyositis With or Without Anti-Melanoma Differentiation-Associated Gene 5 Antibodies:Common Interferon Signature but Distinct NOS2 Expression [J].Am J Pathol,2016,186:691-700.
[16] Kishaba T,McGill R,Nei Y,et al.Clinical characteristics of dermatomyosits/polymyositis associated interstitial lung disease according to the autoantibody [J].J Med Invest,2018,65:251-257.
[17] Gonzalez-Moreno J,Raya-Cruz M,Losada-Lopez I,et al.Rapidly progressive interstitial lung disease due to anti-MDA5 antibodies without skin involvement:a case report and literature review [J].Rheumatol Int,2018,38:1293-1296.
[18] Tamai K,Tachikawa R,Otsuka K,et al.Early pulmonary involvement of anti-CADM-140 autoantibody-positive rapidly progressive interstitial lung disease preceding typical cutaneous symptoms [J].Intern Med,2014,53:2515-2519.
[19] Ortiz-Santamaria V,Babot A,Ferrer C.Anti-MDA5-positive dermatomyositis:an emerging entity with a variable clinical presentation [J].Scand J Rheumatol,2017,46:509-511.
[20] Betteridge Z,McHugh N.Myositis-specific autoantibodies:an important tool to support diagnosis of myositis [J].J Intern Med,2016,280:8-23.
[21] Kurasawa K,Arai S,Namiki Y,et al.Tofacitinib for refractory interstitial lung diseases in anti-melanoma differentiation-associa-ted 5 gene antibody-positive dermatomyositis [J].Rheumatology (Oxford),2018,57:2114-2119.
[22] Fujiki Y,Kotani T,Isoda K,et al.Evaluation of clinical prognostic factors for interstitial pneumonia in anti-MDA5 antibody-positive dermatomyositis patients [J].Mod Rheumatol,2018,28:133-140.
[23] Sato S,Kuwana M,Fujita T,et al.Anti-CADM-140/MDA5 autoantibody titer correlates with disease activity and predicts disease outcome in patients with dermatomyositis and rapidly progressive interstitial lung disease [J].Mod Rheumatol,2013,23:496-502.
[24] Muro Y,Sugiura K,Hoshino K,et al.Disappearance of anti-MDA-5 autoantibodies in clinically amyopathic DM/interstitial lung disease during disease remission [J].Rheumatology (Oxford),2012,51:800-804.
[25] Le Goff B,Cherin P,Cantagrel A,et al.Pneumomediastinum in interstitial lung disease associated with dermatomyositis and polymyositis [J].Arthritis Rheum,2009,61:108-118.
[26] Ma X,Chen Z,Hu W,et al.Clinical and serological features of patients with dermatomyositis complicated by spontaneous pneumomediastinum [J].Clin Rheumatol,2016,35:489-493.
[27] 曹华,郑捷,夏群力等.皮肌炎中抗MDA5抗体阳性患者的临床特点 [C].In:第二届全国皮肤病与性病学博士生学术会议论文集.黄山,2012:167-176.
[28] Marie I,Lahaxe L,Benveniste O,et al.Long-term outcome of patients with polymyositis/ dermatomyositis and anti-PM-Scl antibody [J].Br J Dermatol,2010,162:337-344.
[29] Bonnefoy O,Ferretti G,Calaque O,et al.Serial chest CT findings in interstitial lung disease associated with polymyositis-dermatomyositis [J].Eur J Radiol,2004,49:235-244.
[30] Arakawa H,Yamada H,Kurihara Y,et al.Nonspecific interstitial pneumonia associated with polymyositis and dermatomyositis:serial high-resolution CT findings and functional correlation [J].Chest,2003,123:1096-1103.
[31] Ichikado K,Suga M,Muranaka H,et al.Prediction of prognosis for acute respiratory distress syndrome with thin-section CT:validation in 44 cases [J].Radiology,2006,238:321-329.
[32] Ichikado K,Suga M,Muller NL,et al.Acute interstitial pneumonia:comparison of high-resolution computed tomography findings between survivors and nonsurvivors [J].Am J Respir Crit Care Med,2002,165:1551-1556.
[33] 邹静.临床无肌病型皮肌炎合并急性间质性肺病预后相关危险因素及中性粒细胞、Th17细胞在疾病发病机制中作用的研究[D].In:上海交通大学,2015.
[34] Park JH,Kari S,King LE,Jr.,et al.Analysis of 31P MR spectroscopy data using artificial neural networks for longitudinal evaluation of muscle diseases:dermatomyositis[J].NMR Biomed,1998,11:245-256.
[35] Chino H,Sekine A,Baba T,et al.Radiological and pathological correlation in anti-MDA5 antibody-positive interstitial lung disease:rapidly progressive perilobular opacities and diffuse alveolar damage[J].Intern Med,2016,55:2241-2246.
[36] Cox NH.Amyopathic dermatomyositis,photosensitivity and hydroxychloroquine[J].Br J Dermatol,1995,132:1016-1017.
[37] Hornung T,Ko A,Tuting T,et al.Efficacy of low-dose methotrexate in the treatment of dermatomyositis skin lesions[J].Clin Exp Dermatol,2012,37:139-142.
[38] Tsujimura S,Saito K,Tanaka Y.Complete resolution of dermatomyositis with refractory cutaneous vasculitis by intravenous cyclophosphamide pulse therapy[J].Intern Med,2008,47:1935-1940.
[39] Dinh HV,McCormack C,Hall S,et al.Rituximab for the treatment of the skin manifestations of dermatomyositis:a report of 3 cases[J].J Am Acad Dermatol,2007,56:148-153.
[40] Flores-Suarez LF,Morales H,Angeles A,et al.Drug-induced amyopathic dermatomyositis[J].J Clin Rheumatol,2002,8:50-54.
[41] Marco Puche A,Calvo Penades I,Lopez Montesinos B.Effectiveness of the treatment with intravenous pamidronate in calcinosis in juvenile dermatomyositis[J].Clin Exp Rheumatol,2010,28:135-140.
[42] 叶霜,黄文群,吴美芳,等.以急进性肺间质病变为突出表现的无肌炎的皮肌炎[J].中华风湿病学杂志,2006,10:527-533.
[43] Kurita T,Yasuda S,Amengual O,et al.The efficacy of calcineurin inhibitors for the treatment of interstitial lung disease associated with polymyositis/dermatomyositis[J].Lupus,2015,24:3-9.
[44] 郭强,照日格图,吴美芳,等.伴急性/亚急性间质性肺炎的临床无肌炎皮肌炎1年生存随访及危险因素分析[J].上海医学,2009,32:860-864,封862.
[45] Miyazaki E,Ando M,Muramatsu T,et al.Early assessment of rapidly progressive interstitial pneumonia associated with amyopathic dermatomyositis[J].Clin Rheumatol,2007,26:436-439.
[46] Ando M,Miyazaki E,Yamasue M,et al.Successful treatment with tacrolimus of progressive interstitial pneumonia associated with amyopathic dermatomyositis refractory to cyclosporine[J].Clin Rheumatol,2010,29:443-445.
[47] Yamasaki Y,Yamada H,Yamasaki M,et al.Intravenous cyclophosphamide therapy for progressive interstitial pneumonia in patients with polymyositis/dermatomyositis[J].Rheumatology (Oxford),2007,46:124-130.
[48] Nawata Y,Kurasawa K,Takabayashi K,et al.Corticosteroid resistant interstitial pneumonitis in dermatomyositis/polymyositis:prediction and treatment with cyclosporine[J].J Rheumatol,1999,26:1527-1533.
[49] Barnes H,Holland AE,Westall GP,et al.Cyclophosphamide for connective tissue disease-associated interstitial lung disease[J].Cochrane Database Syst Rev,2018,1:Cd010908.
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