Torres-Ruiz Jiram, Carrillo-Vazquez Daniel Alberto, Padilla-Ortiz Diana Marcela, Vazquez-Rodriguez Ricardo, Nuñez-Alvarez Carlos, Juarez-Vega Guillermo, Gomez-Martin Diana
Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Emergency Medicine Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
J Transl Med. 2020 Mar 12;18(1):125. doi: 10.1186/s12967-020-02290-3.
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.
在特发性炎性肌病（IIM）患者的肌肉活检炎性浸润中发现了单核细胞和Toll样受体（TLR），提示这些细胞在肌炎发病机制中起重要作用。IIM患者外周血中的单核细胞亚群、其TLR表达及其与临床特征的关系尚未得到研究。
我们招募了45例确诊为IIM的患者和15名年龄及性别匹配的健康对照。我们评估了疾病活动度和损伤情况，进行了甲襞毛细血管镜检查，并从病历中记录了心肺参数。通过流式细胞术评估单核细胞亚群、其TLR2和TLR4的表达以及血清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）或最小值和最大值（min-max）。组间差异采用Mann-Whitney U检验和Kruskal-Wallis检验进行评估。定量变量之间的相关性采用Spearman Rho检验进行评估。
29例患者为女性（64.4%），32例（71.1%）患有皮肌炎。与健康对照相比，活动性IIM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患者所有单核细胞亚群中的TLR4表达均较高，与疾病活动度和泼尼松治疗无关。血清IL-6与每个单核细胞亚群中的TLR2表达相关，吞咽困难患者中间单核细胞中的TLR2表达更高。甲襞毛细血管镜检查异常的受试者中TLR2+经典和非经典单核细胞数量更多，间质性肺疾病（ILD）患者中TLR4+非经典单核细胞百分比更高。抗Mi2抗体阳性患者的经典和中间单核细胞中TLR4表达更高。中间单核细胞百分比和所有单核细胞亚群中TLR4的表达在IIM患者中具有良好的诊断能力。
IIM患者的单核细胞亚群组成不同，TLR2和TLR4表达增强，这与疾病活动度以及包括吞咽困难、ILD、血管病变和促炎细胞因子在内的独特临床特征相关。这些免疫学特征可能作为IIM潜在的诊断工具以及新的疾病活动生物标志物。
