Biomarkers in Systemic Sclerosis

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by vasculopathy, immune dysregulation, and progressive fibrosis affecting the skin and internal organs. Pulmonary complications, including interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), are major contributors to morbidity and mortality, while skin fibrosis remains a hallmark of disease heterogeneity. Despite advances in understanding SSc pathogenesis, early diagnosis and timely therapeutic intervention remain challenging due to the rapid progression of inflammation and the narrow window before irreversible fibrosis occurs. The identification of reliable biomarkers is crucial for improving diagnosis, monitoring disease activity, and guiding treatment decisions in SSc. While autoantibodies are well-established diagnostic tools, this review focused on non-autoantibody biomarkers, including soluble proteins, cytokines, chemokines, epigenetic modifiers, and oxidative stress indicators. These biomarkers reflect diverse pathogenic mechanisms such as endothelial injury, fibroblast activation, immune signaling, and extracellular matrix remodeling. By examining the available evidence across both clinical and preclinical studies, this review provides an updated overview of molecular markers involved in inflammation and fibrosis in SSc. Understanding their biological significance and therapeutic potential may improve risk stratification, guide targeted interventions, and ultimately contribute to the development of precision medicine strategies in systemic sclerosis.