TLR expression in peripheral monocyte subsets of patients with idiopathic inflammatory myopathies: association with clinical and immunological features

被引:17
作者
Torres-Ruiz, Jiram [1 ,2 ]
Carrillo-Vazquez, Daniel Alberto [1 ]
Padilla-Ortiz, Diana Marcela [1 ,3 ]
Vazquez-Rodriguez, Ricardo [1 ]
Nunez-Alvarez, Carlos [1 ]
Juarez-Vega, Guillermo [4 ]
Gomez-Martin, Diana [5 ]
机构
[1] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City, DF, Mexico
[2] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Emergency Med, Mexico City, DF, Mexico
[3] Univ La Sabana, Hosp Mil Cent, Bogota, DC, Colombia
[4] Univ Nacl Autonoma Mexico, Flow Cytometry Unit, Red Apoyo Invest, Coordinac Invest Cient, Mexico City, DF, Mexico
[5] Tecnol Monterrey, Escuela Med & Ciencias Salud, Ave Morones Prieto 3000, Monterrey 64710, Nuevo Leon, Mexico
关键词
Dermatomyositis; Monocytes; TLR4; TLR2; TOLL-LIKE RECEPTORS; INTERMEDIATE MONOCYTES; NONCLASSICAL MONOCYTES; BLOOD MONOCYTES; MODEL; DERMATOMYOSITIS; POLYMYOSITIS; ARTHRITIS; MYOSITIS; TAK-242;
D O I
10.1186/s12967-020-02290-3
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background 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. Methods 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. Results 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. Conclusion 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.
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页数:12
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