Differential modulations of miRNAs in patients with systemic sclerosis-associated skeletal muscle loss

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.