Monocytes and toll-like receptors (TLR) have been found in the inflammatory infiltrate of muscle biopsies in patients with idiopathic inflammatory myopathies (IIM), suggesting an important role of these cells in the pathogenesis of myositis. The monocyte subsets, their TLR expression in peripheral blood and their relationship with the clinical characteristics of patients with IIM has not been addressed. We recruited 45 patients with IIM diagnosis and 15 age and sex-adjusted healthy controls. We assessed the disease activity and damage, performed a nailfold capillaroscopy and registered the cardio-pulmonary parameters from the medical charts. Monocyte subsets, their expression of TLR2 and TLR4 and the serum Th1/Th2/Th17 cytokines levels were evaluated by flow cytometry. We expressed quantitative variables as medians and interquartile ranges (IQR) or minimum and maximum (min–max). Differences between groups were assessed with Mann–Whitney U and the Kruskal–Wallis tests. Correlation between quantitative variables was assessed with Spearman Rho. Twenty-nine patients were women (64.4%) and 32 (71.1%) had dermatomyositis. In comparison to healthy controls, patients with active IIM had a higher percentage of intermediate monocytes and lower amounts of classical monocytes. Patients with IIM had a higher expression of TLR4 in all their monocyte subsets, regardless of disease activity and prednisone treatment. Serum IL-6 correlated with the TLR2 expression in every monocyte subset and the expression of TLR2 in intermediate monocytes was higher among patients with dysphagia. Subjects with nailfold capillaroscopy abnormalities had a higher amount of TLR2+ classical and non-classical monocytes and those with interstitial lung disease (ILD) had a higher percentage of TLR4+ non-classical monocytes. The classical and intermediate monocytes from patients with anti Mi2 antibodies had a higher expression of TLR4. The percentage of intermediate monocytes and the expression of TLR4 in all monocyte subsets showed a good diagnostic capacity in patients with IIM. Patients with IIM have a differential pool of monocyte subsets with an enhanced expression of TLR2 and TLR4, which correlates with disease activity and distinctive clinical features including dysphagia, ILD, vasculopathy, and pro-inflammatory cytokines. These immunological features might be useful as a potential diagnostic tool as well as novel disease activity biomarkers in IIM.

中文翻译：

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特发性炎症性肌病患者外周单核细胞亚群中的TLR表达：与临床和免疫学特征相关。

在患有特发性炎性肌病（IIM）的患者的肌肉活检组织的炎性浸润中已发现单核细胞和toll样受体（TLR），表明这些细胞在肌炎的发病机理中具有重要作用。还没有解决单核细胞亚群，它们在外周血中的TLR表达以及它们与IIM患者临床特征的关系。我们招募了45位具有IIM诊断的患者和15位经过年龄和性别调整的健康对照。我们评估了疾病的活动性和损伤，进行了折叠式毛细血管镜检查并从医学图表中记录了心肺参数。通过流式细胞术评估单核细胞亚群，它们的TLR2和TLR4表达以及血清Th1 / Th2 / Th17细胞因子水平。我们将定量变量表示为中位数和四分位间距（IQR）或最小和最大（min-max）。使用Mann–Whitney U和Kruskal–Wallis检验评估组之间的差异。定量变量之间的相关性用Spearman Rho评估。二十九例患者为女性（64.4％），其中三十二例（71.1％）患有皮肌炎。与健康对照组相比，IIM活跃患者的中间单核细胞百分比更高，经典单核细胞数量更低。IIM患者在所有单核细胞亚群中均具有较高的TLR4表达，而与疾病活动和强的松治疗无关。吞咽困难患者中，血清IL-6与每个单核细胞亚群中的TLR2表达相关，并且中间单核细胞中TLR2的表达较高。指甲折叠毛细血管镜检查异常患者的TLR2 +经典和非经典单核细胞数量较多，而间质性肺病（ILD）患者的TLR4 +非经典单核细胞百分比更高。来自抗Mi2抗体患者的经典和中间单核细胞具有较高的TLR4表达。IIM患者的中间单核细胞百分比和所有单核细胞亚群中TLR4的表达均具有良好的诊断能力。IIM患者的单核细胞亚群差异明显，TLR2和TLR4表达增强，这与疾病活动和吞咽困难，ILD，血管病变和促炎性细胞因子等独特的临床特征相关。