A Potential Contribution of S100A11 to Skin Fibrosis and Pulmonary Involvement in Systemic Sclerosis

ABSTRACT Systemic sclerosis (SSc) is characterised by immune dysregulation, vasculopathy and fibrosis, driven by genetic and environmental factors. S100 proteins, which constitute a unique class of calcium‐binding proteins, have been shown to be critically implicated in various inflammatory and fibrotic conditions. In this study, we investigated the possible involvement of S100A11 in SSc by examining its cutaneous expression and systemic serum levels, correlating them with key clinical parameters. First, we performed immunohistochemical (IHC) staining to examine S100A11 localisation in skin specimens from SSc patients and controls, and found that S100A11 was robustly expressed in SSc dermal fibroblasts. Analysis on the publicly available single‐cell RNA‐sequencing (scRNA‐seq) data of SSc skin samples further confirmed that S100A11 was highly expressed in SSc dermal fibroblasts along with several key genes associated with cellular senescence. Finally, we evaluated serum levels of S100A11 in SSc patients and HCs using enzyme‐linked immunosorbent assay (ELISA), and found that serum S100A11 levels were significantly elevated in diffuse cutaneous SSc (dcSSc) patients compared to controls. S100A11 serum levels in SSc patients were significantly correlated with modified Rodnan total skin thickness score and key parameters of SSc‐related interstitial lung disease. Our data collectively suggested a potential pathophysiological role of S100A11 in the cutaneous and lung fibrosis associated with SSc, warranting further investigation into its functional roles in this disease.