Tambaro Federica, Gigante Antonietta, Gallicchio Carmen, Pellicano Chiara, Ramaccini Cesarina, Belli Roberta, Gasperini-Zacco Maria Ludovica, Rosato Edoardo, Muscaritoli Maurizio
Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
Experimental Immunology Laboratory, Istituto Dermopatico dell'Immacolata (IDI-IRCCS), Rome, Italy.
Eur J Intern Med. 2025 May;135:98-107. doi: 10.1016/j.ejim.2025.03.034. Epub 2025 Apr 2.
Systemic sclerosis (SSc) is an autoimmune disease characterized by sustained vascular inflammation and progressive skin and internal organs fibrosis. Up to 22 % of SSc patients may manifest skeletal muscle impairment, which predicts worse clinical outcomes, including increased mortality, however, pathogenesis is still largely unclear and could be associated with modulation of circulating microRNAs (miRNAs). Aims of the present study were to evaluate differentially modulated miRNAs in SSc patients and to evaluate their association with changes in body composition(s) and with the clinical course and type of the disease.
Circulating levels of miRNAs were detected by RT-qPCR. ELISA assay was performed to measure the TGF-β1 protein. Muscularity (FFMI kg/m2) and phase angle (PhA, °) were estimated by Bioelectrical Impedance Analysis.
We enrolled 47 SSc patients and 21 controls (C). We observed downregulation of miR-15b (p = 0.024), -21 (p < 0.001), -29a (p < 0.001), -29b (p = 0.007) and -133a (p < 0.001), whereas miR-206 (p < 0.001) and -486 (p < 0.001) were upregulated in SSc vs C. In SSc, miR-29b negatively correlates with TGF-β1 (r = -0.303, p = 0.046). MiR-206 was downregulated vs high FFMI (p = 0.040) in SSc with low FFMI, and miR-15b positively correlates with PhA (r = 0.356, p = 0.014). MiR-15b and -486 were modulated in early vs late nailfold capillaroscopy stage (p = 0.028 and p = 0.045, respectively). MiR-133a was higher in SSc with Scl70 v ACA subset of autoantibodies (p = 0.002).
In SSc patients, differential modulations of miRNAs involved in muscularity occur. The data obtained suggest that mechanisms other than disease-related malnutrition might be responsible for SSc-associated skeletal muscle loss.
系统性硬化症（SSc）是一种自身免疫性疾病，其特征为持续性血管炎症以及进行性皮肤和内脏器官纤维化。高达22%的SSc患者可能出现骨骼肌损伤，这预示着更差的临床结局，包括死亡率增加，然而，其发病机制仍 largely不清楚，可能与循环微小RNA（miRNA）的调节有关。本研究的目的是评估SSc患者中差异调节的miRNA，并评估它们与身体成分变化、疾病临床进程和类型的关联。
通过RT-qPCR检测miRNA的循环水平。采用ELISA法检测TGF-β1蛋白。通过生物电阻抗分析评估肌肉量（FFMI kg/m2）和相位角（PhA，°）。
我们纳入了47例SSc患者和21例对照（C）。我们观察到miR-15b（p = 0.024）、-21（p < 0.001）、-29a（p < 0.001）、-29b（p = 0.007）和-133a（p < 0.001）下调，而与对照相比，SSc患者中miR-206（p < 0.001）和-486（p < 0.001）上调。在SSc中，miR-29b与TGF-β1呈负相关（r = -0.303，p = 0.046）。在FFMI低的SSc患者中，与高FFMI相比，miR-206下调（p = 0.040），且miR-15b与PhA呈正相关（r = 0.356，p = 0.014）。在甲襞毛细血管镜检查的早期与晚期阶段，miR-15b和-486受到调节（分别为p = 0.028和p = 0.045）。在抗Scl70抗体与抗ACA抗体亚组的SSc患者中，miR-133a更高（p = 0.002）。
在SSc患者中，参与肌肉量的miRNA存在差异调节。获得的数据表明，除了疾病相关的营养不良之外，其他机制可能是SSc相关骨骼肌丢失的原因。
