Association of circulating miR-29b with microvascular dysfunction and digital ulcers in patients with systemic sclerosis: a single-centre pilot study.

OBJECTIVES: Systemic sclerosis is a rare autoimmune disorder marked by vasculopathy, immune dysregulation, and progressive fibrosis. Digital ulcers (DUs) reflect severe microvascular dysfunction. This pilot, single-centre, observational study investigated whether circulating miR-29b is associated with DU occurrence, recurrence, and microvascular impairment. METHODS: Twenty-nine patients with systemic sclerosis and 17 healthy controls (HC) were evaluated. Clinical data, including DU history and recurrence, were collected. Cutaneous blood perfusion was assessed by laser speckle contrast analysis (LASCA), and proximal-distal gradient was calculated as perfusion difference between distal and proximal finger regions. Nailfold videocapillaroscopy classified microangiopathy as early, active, or late, while renal resistive index (RRI) served as an additional systemic vascular marker. Circulating miR-29b was quantified by RT-qPCR. RESULTS: Different modulation of miR-29b were observed between SSc and C (p<0.001). Patients with previous or recurrent DUs (p=0.024) and those with proximal-distal gradient <30 perfusion units showed significantly reduced miR-29b levels (p=0.028). Lower expression also characterised patients with RRI > 0.70 (p=0.03) and a late pattern (p<0.01). MiR-29b inversely correlated with disease activity (r=-0.472, p<0.01), fibrosis extent (r=-0.471, p<0.01), Cochin hand function score (r=-0.454, p<0.01), and RRI (r=-0.506, p<0.01), while showing a positive correlation with disease duration (r=0.333, p<0.05). In exploratory multivariable Cox regression analysis, lower miR-29b remained an independently associated with DU recurrence (p<0.05). CONCLUSIONS: Overall, reduced circulating miR-29b was associated with advanced digital vasculopathy. Combined evaluation with LASCA-derived proximal-distal gradient and NVC pattern could may provide exploratory information for microvascular dysfunction and stratify patients at high risk of vascular complications.