From the Departments of Clinical Immunology and Internal Medicine (Y.A., S.T., G.L., B.H., N.C., K.M., O.B.), Immunobiology (M.M.), and Biostatistics, Public Health, and Medical Information (B.G.), Pitié-Salpêtrière Hospital, APHP, Sorbonne Universities; Myology Research Centre (Y.A., O.B.), INSERM, UMRS 974, Paris; Department of Pneumology (Y.U., H.N.), APHP, Avicenne Hospital, INSERM U1272, Université Sorbonne Paris Nord, Bobigny; Department of Internal Medicine (L.G., A. Marquet), Lyon Sud Hospital, Lyon Sud University, Paris; Reference Centre for Rare Autoimmune Diseases (A. Meyer) and Medical Intensive Care Unit, Hautepierre Hospital (V. Castelain), Hôpitaux Universitaires de Strasbourg, Strasbourg University; Division of Pneumology (R.B.), Bichat Hospital, AP-HP, Paris-Diderot University, Paris; Department of Pneumology (F.G., P.P.), Centre Hospitalier Universitaire, Angers University; Department of Internal Medicine Infectieuses (C.D.), CHU de Martinique, Fort de France; Departments of Internal Medicine and Clinical Immunology (S.A.) and Internal Medicine and Systemic Diseases (H.D.), François-Mitterrand University Hospital, University of Bourgogne-Franche-Comté, Dijon; Internal Medicine Department (B.T., A.B.), Cochin Hospital, AP-HP, René Descartes University, Paris; Department of Internal Medicine (C.G., N.L.), Henri Mondor Hospital, Paris Est Créteil University, Créteil, France; Department of Neurology (N.V.), Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Centre, Nijmegen, the Netherlands; Department of Internal Medicine (E.D.), Hôpital Bretonneau Tours, Tours University; Internal Medicine Department (A.S.), Hôpital Robert-Debré, Reims University; Departments of Rheumatology (T.M.) and Internal Medicine (L.D.S.M.), Bretagne Occidentale University, Centre Hospitalo-Universitaire de Brest; Department of Internal Medicine (S.H.), CHU de Besançon; Department of Internal Medicine (C.B.-D.), Centre Hospitalier Général de Niort; Department of Internal Medicine (N.T.), Nice University, CHU Nice; Department of Internal Medicine (P.C.), Institut Mutualiste Montsouris, Paris; Department of Internal Medicine (M.G.), Jean Verdier Hospital, Paris Seine-Saint-Denis University, Bondy; Department of Internal Medicine (A. Mekinian), Saint Antoine Hospital, APHP, Sorbonne Universities, Paris; Department of Pneumology CHU (J.C.M.), Poitiers University; Department of Pneumology (A.T.), Hôpital Saint-Louis, APHP, Sorbonne Paris Cité, University Paris-Diderot, Paris; Department of Respiratory Medicine (V. Cottin), National Reference Center for Rare Pulmonary Diseases, Hospices Civils de Lyon, Claude Bernard University Lyon 1, Lyon University; Department of Pneumology (D.I.-B.), European George Pompidou Hospital, APHP, Paris V University; Department of Pneumology (S.P.-H.), Sainte-Camille Hospital, Bry-sur-Marne; Department of Pneumology (C.B.), Foch Hospital, Saint Quentin en Yveline University, Suresnes; and Department of Immunology (N.F.), Lyon-Sud Hospital, Hospices Civils-de-Lyon, Pierre-Bénite, France.
Neurology. 2020 Jul 7;95(1):e70-e78. doi: 10.1212/WNL.0000000000009727. Epub 2020 Jun 2.
The predominance of extramuscular manifestations (e.g., skin rash, arthralgia, interstitial lung disease [ILD]) as well as the low frequency of muscle signs in anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5+) dermatomyositis caused us to question the term myositis-specific antibody for the anti-MDA5 antibody, as well as the homogeneity of the disease.
To characterize the anti-MDA5+ phenotype, an unsupervised analysis was performed on anti-MDA5+ patients (n = 83/121) and compared to a group of patients with myositis without anti-MDA5 antibody (anti-MDA5-; n = 190/201) based on selected variables, collected retrospectively, without any missing data.
Within anti-MDA5+ patients (n = 83), 3 subgroups were identified. One group (18.1%) corresponded to patients with a rapidly progressive ILD (93.3%; < 0.0001 across all) and a very high mortality rate. The second subgroup (55.4%) corresponded to patients with pure dermato-rheumatologic symptoms (arthralgia; 82.6%; < 0.01) and a good prognosis. The third corresponded to patients, mainly male (72.7%; < 0.0001), with severe skin vasculopathy, frequent signs of myositis (proximal weakness: 68.2%; < 0.0001), and an intermediate prognosis. Raynaud phenomenon, arthralgia/arthritis, and sex permit the cluster appurtenance (83.3% correct estimation). Nevertheless, an unsupervised analysis confirmed that anti-MDA5 antibody delineates an independent group of patients (e.g., dermatomyositis skin rash, skin ulcers, calcinosis, mechanic's hands, ILD, arthralgia/arthritis, and high mortality rate) distinct from anti-MDA5- patients with myositis.
Anti-MDA5+ patients have a systemic syndrome distinct from other patients with myositis. Three subgroups with different prognosis exist.
抗黑色素瘤分化相关基因 5 抗体阳性（抗 MDA5+）皮肌炎中肌肉外表现（如皮疹、关节炎、间质性肺病[ILD]）较为常见，肌肉表现较少，这使我们对 MDA5 抗体的肌炎特异性抗体这一术语以及疾病的同质性产生了质疑。
为了描述抗 MDA5+患者的表型，我们对 83/121 例抗 MDA5+患者进行了无监督分析，并与一组无抗 MDA5 抗体的肌炎患者（抗 MDA5-；n=190/201）进行了比较，所选变量均为回顾性收集，无任何缺失数据。
在抗 MDA5+患者（n=83）中，确定了 3 个亚组。一组（18.1%）对应于ILD 迅速进展的患者（93.3%；所有患者均<0.0001），死亡率非常高。第二组（55.4%）对应于仅有皮肌炎症状的患者（关节炎；82.6%；<0.01），预后良好。第三组对应于主要为男性（72.7%；<0.0001）的患者，有严重的皮肤血管病变，常伴有肌炎表现（近端肌无力：68.2%；<0.0001），预后中等。雷诺现象、关节炎/关节痛和性别可用于确定聚类归属（83.3%的正确估计）。然而，无监督分析证实抗 MDA5 抗体可划出一个与抗 MDA5-肌炎患者不同的独立患者群体（如皮肌炎皮疹、皮肤溃疡、钙质沉着、技工手、ILD、关节炎/关节痛和高死亡率）。
抗 MDA5+患者的系统性综合征与其他肌炎患者不同。存在预后不同的 3 个亚组。
