Development of a New Classification System for Idiopathic Inflammatory Myopathies Based on Clinical Manifestations and Myositis-Specific Autoantibodies
Development of a New Classification System for Idiopathic Inflammatory Myopathies Based on Clinical Manifestations and Myositis-Specific Autoantibodies
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DOI：
10.1001/jamaneurol.2018.2598
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发表时间：
2018-12-01
期刊：
影响因子：
29
通讯作者：
Benveniste, Olivier
中科院分区：
文献类型：
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作者：
Mariampillai, Kuberaka;Granger, Benjamin;Benveniste, Olivier
重要性 特发性炎症性肌病的病理生理学特征和预后各不相同。肌炎特异性自身抗体的出现表明存在患者亚组。 目的 根据表型、生物学和免疫学标准制定特发性炎症性肌病的新分类方案。 设计、设置和参与者 使用法国肌炎网络数据库进行了一项观察性、回顾性队列研究。 2003年1月1日至2016年2月1日期间，神经肌肉疾病转诊中心确定的患者被纳入研究。在445名初始患者中，排除了185名患者，并纳入了260名成年肌炎患者，这些患者拥有完整的数据并明确了多发性肌炎、皮肌炎和包涵体肌炎的历史分类。所有患者均接受了抗组氨酰ARN-t-合成酶（Jot）、抗苏氨酸-ARN-t-合成酶（PL7）、抗丙氨酸-ARN-t-合成酶（PL12）、抗复合物核小体重塑组蛋白脱乙酰酶（Mi2）、抗Ku、抗多发性肌炎/系统性硬皮病的检测 (PMScI)、抗拓扑异构酶 1(Scl70) 和抗信号识别颗粒 (SRP) 抗体。每名患者总共收集了 708 个变量（例如，癌症、肺部受累和肌炎特异性抗体）。 主要结果和测量 无监督多重对应分析和层次聚类分析，将患者分组为亚组。 结果 260 名参与者（163 [62.7%] 女性；平均年龄，59.7 岁；中位年龄[范围]，61.5 岁） [48-71岁]），出现了4组患者。第 1 组（n = 77）包括年龄超过 60 岁的男性、白人、手指屈肌和股四头肌无力以及空泡纤维和线粒体异常的患者。第 1 类重组了患有包涵体肌炎的患者（77 名患者中的 72 名 [93.5%]；95% CI，85.5%-97.8%；P < .001）。第 2 组 (n = 91) 重新分组的患者为女性，她们具有高肌酸磷酸激酶水平、无炎症的坏死以及与免疫介导的坏死性肌病相对应的抗 SRP 或抗 3-羟基-3-甲基戊二酰辅酶 A 还原酶 (HMGCR) 抗体（91 例中的 53 例[58.2%]；95% 置信区间，47.4%-68.5%； P < .001)。第 3 组 (n = 52) 重新分组了患有皮肌炎皮疹和抗 Mi2、抗黑色素瘤分化相关蛋白 5 (MDAS) 或抗转录中间因子 (TIFly) 抗体的患者，主要对应于患有皮肌炎的患者（52 名患者中的 43 名 [82.7%1 95% CI，69.7%-91.8%；P < .001）。簇 4 (n = 40) 的定义是存在对应于抗合成酶综合征的抗 Jot 或抗 PL7 抗体（40 例中有 36 例 [90.0%]；95% CI，76.3%-97.2%；P < .001）。独立队列 (n = 50) 的分类证实了 4 个簇（Cohen K light，0.8；95% CI，0.6-0.9）。结论和相关性这些研究结果表明特发性炎症性肌病分为 4 个亚组：皮肌炎、包涵体肌炎、免疫介导的坏死性肌病和抗合成酶 综合症。该分类系统表明，可能需要采用有针对性的临床血清学方法来识别特发性炎症性肌病。
IMPORTANCE Idiopathic inflammatory myopathies are heterogeneous in their pathophysiologic features and prognosis. The emergence of myositis-specific autoantibodies suggests that subgroups of patients exist.OBJECTIVE To develop a new classification scheme for idiopathic inflammatory myopathies based on phenotypic, biological, and immunologic criteria.DESIGN, SETTING, AND PARTICIPANTS An observational, retrospective cohort study was performed using a database of the French myositis network. Patients identified from referral centers for neuromuscular diseases were included from January 1, 2003, to February 1, 2016. Of 445 initial patients, 185 patients were excluded and 260 adult patients with myositis who had complete data and defined historical classifications for polymyositis, dermatomyositis, and inclusion body myositis were enrolled. All patients were tested for anti-histidyl-ARN-t-synthetase (Jot), anti-threonine-ARN-t-synthetase (PL7), anti-alanine-ARN-t-synthetase (PL12), anti-complex nucleosome remodeling histone deacetylase (Mi2), anti-Ku, anti-polymyositis/systemic scleroderma (PMScI), anti-topoisomerase 1(Scl70), and anti-signal recognition particle (SRP) antibodies. A total of 708 variables were collected per patient (eg, cancer, lung involvement, and myositis-specific antibodies).MAIN OUTCOMES AND MEASURES Unsupervised multiple correspondence analysis and hierarchical clustering analysis to aggregate patients in subgroups.RESULTS Among 260 participants (163 [62.7%] women; mean age, 59.7 years; median age [range], 61.5 years [48-71 years]), 4 clusters of patients emerged. Cluster 1(n = 77) included patients who were male, white, and older than 60 years and had finger flexor and quadriceps weakness and findings of vacuolated fibers and mitochondrial abnormalities. Cluster 1 regrouped patients who had inclusion body myositis (72 of 77 patients [93.5%]; 95% CI, 85.5%-97.8%; P < .001). Cluster 2 (n = 91) regrouped patients who were women and had high creatine phosphokinase levels, necrosis without inflammation, and anti-SRP or anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies corresponding to immune-mediated necrotizing myopathy (53 of 91[58.2%]; 95% CI, 47.4%-68.5%; P < .001). Cluster 3 (n = 52) regrouped patients who had dermatomyositis rash and anti-Mi2, anti-melanoma differentiation-associated protein 5 (MDAS), or anti-transcription intermediary factor-ly (TIFly) antibodies, mainly corresponding with patients who had dermatomyositis (43 of 52 [82.7%1 95% CI, 69.7%-91.8%; P < .001). Cluster 4 (n = 40) was defined by the presence of anti-Jot or anti-PL7 antibodies corresponding to antisynthetase syndrome (36 of 40 [90.0%]; 95% CI, 76.3%-97.2%; P < .001). The classification of an independent cohort (n = 50) confirmed the 4 clusters (Cohen K light, 0.8; 95% CI, 0.6-0.9).CONCLUSIONS AND RELEVANCE These findings suggest a classification of idiopathic inflammatory myopathies with 4 subgroups: dermatomyositis, inclusion body myositis, immune-mediated necrotizing myopathy, and antisynthetase syndrome. This classification system suggests that a targeted clinical-serologic approach for identifying idiopathic inflammatory myopathies may be warranted.