Objectives DM and clinically amyopathic DM (CADM) patients with positive expression of anti-transcription intermediary factor 1-γ (anti-TIF1-γ) antibody (Ab) are characterized by distinct clinicopathological features. We aimed to determine the role of cytokine/chemokine profiles in the classification of anti-TIF1-γ positive DM/CADM patients. Methods Serum levels of 24 cytokines/chemokines were measured in 27 anti-TIF1-γ positive DM/CADM patients by a Luminex 200 system. Principal components analysis and unsupervised hierarchical clustering were used to reduce variables and establish patient subgroups. Spearman’s correlation coefficient was calculated between cytokine/chemokine levels and disease activity markers. Results Among anti-TIF1-γ positive DM/CADM patients, two distinct patient clusters were identified. The diagnosis of CADM was more common in cluster 1 than in cluster 2 (58.3% vs 6.7%, P = 0.008). Skin disease activity was higher in cluster 2 than in cluster 1 as measured by Cutaneous DM Disease Area and Severity Index–Activity [38.6 (10.4) vs 25.3 (10.0), P = 0.003]. Patients within cluster 2 exhibited significant muscle weakness (Medical Research Council scale ≤ 3, 33.3% vs 0.0%, P = 0.047), higher levels of anti-TIF1-γ Ab [92.4 (20.6) vs 66.9 (13.9), P = 0.001] and an increased malignancy rate (73.3% vs 25.0%, P = 0.021). Cluster 2 exhibited higher serum levels of CXCL10 [564.2 (258.8) vs 122.0 (97.8), P < 0.001], CCL2 [1136.6 (545.4) vs 441.6 (163.3), P < 0.001], galectin-9 [38879.6 (20009.3) vs 12612.4 (6640.0), P < 0.001], IL-18 [436.1 (188.9) vs 243.0 (114.5), P = 0.003], TNF-α [9.3 (3.8) vs 5.6 (2.4), P = 0.007] and TNFRI [1385.1 (338.2) vs 2605.6 (928.5), P < 0.001] than cluster 1. Conclusion In anti-TIF1-γ positive DM/CADM, we identified a ‘skin-predominant’ cluster and a ‘hyperinflammation’ cluster based on the cytokine/chemokine profiles. Cytokine/chemokine profiles in anti-TIF1-γ positive DM/CADM can identify discrete clusters of patients with different disease patterns, organ involvements and clinical outcomes.

中文翻译：

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用抗转录中间因子 1-γ 抗体鉴定皮肌炎中不同的细胞因子/趋化因子谱

目的 抗转录中介因子 1-γ（anti-TIF1-γ）抗体（Ab）阳性表达的 DM 和临床无肌病 DM（CADM）患者具有不同的临床病理特征。我们旨在确定细胞因子/趋化因子谱在抗 TIF1-γ 阳性 DM/CADM 患者分类中的作用。方法 采用 Luminex 200 系统测定 27 例抗 TIF1-γ 阳性 DM/CADM 患者的血清 24 种细胞因子/趋化因子水平。使用主成分分析和无监督层次聚类来减少变量并建立患者亚组。计算细胞因子/趋化因子水平和疾病活动标志物之间的 Spearman 相关系数。结果 在抗 TIF1-γ 阳性 DM/CADM 患者中，确定了两个不同的患者群。CADM 的诊断在集群 1 中比在集群 2 中更常见（58.3% vs 6.7%，P = 0.008）。根据皮肤 DM 疾病面积和严重性指数-活动性测量，第 2 组的皮肤病活动高于第 1 组 [38.6 (10.4) 对 25.3 (10.0)，P = 0.003]。集群 2 中的患者表现出明显的肌肉无力（医学研究委员会评分 ≤ 3, 33.3% vs 0.0%, P = 0.047），抗 TIF1-γ Ab 水平较高 [92.4 (20.6) vs 66.9 (13.9), P = 0.001 ] 和增加的恶性肿瘤率（73.3% vs 25.0%，P = 0.021）。簇 2 表现出更高的 CXCL10 血清水平 [564.2 (258.8) 对比 122.0 (97.8)，P < 0.001]，CCL2 [1136.6 (545.4) 与 441.6 (163.3)，P < 0.001], galectin-9 [38879.6 (20009.3) vs 12612.4 (6640.0), P < 0.001]，IL-18 [436.1 (188.9) vs 243.0 (114.5)，P = 0.003]，TNF-α [9.3 (3.8) vs 5.6 (2.4)，P = 0。007] 和 TNFRI [1385.1 (338.2) 对比 2605.6 (928.5)，P < 0.001] 比簇 1. 结论 在抗 TIF1-γ 阳性 DM/CADM 中，我们根据细胞因子/趋化因子谱确定了一个“皮肤主导”簇和一个“过度炎症”簇。抗 TIF1-γ 阳性 DM/CADM 中的细胞因子/趋化因子谱可以识别具有不同疾病模式、器官受累和临床结果的离散患者群。