Biomarker-based clustering identifies distinct pulmonary function trajectories in early systemic sclerosis

Background: Systemic sclerosis (SSc) is a heterogeneous autoimmune disease in which interstitial lung disease (ILD) is a major determinant of mortality. Given that certain chemokines and adhesion molecules may be involved in the inflammation, subsequent vascular injury, and fibrosis observed in SSc, their circulating levels in peripheral blood may reflect the disease processes ranging from inflammation to vascular damage and fibrotic remodeling. However, the potential of these biomarkers to identify patient subgroups with divergent pulmonary trajectories remains to be elucidated. Methods: We performed a retrospective analysis of prospectively collected data from patients with early severe SSc (diffuse cutaneous SSc irrespective of ILD status or limited cutaneous SSc with ILD; disease duration <5 years) who were enrolled in a multicenter cohort. Serum levels of five chemokines and four soluble adhesion molecules were quantified at baseline. Patients were classified based on these biomarker profiles using k-means clustering. Changes in pulmonary function were compared among clusters using relative changes in percent vital capacity (%VC). Results: = 0.042). These biomarker-defined patterns were consistent with a vasculopathic-fibrotic profile in Cluster 1 and an inflammatory-vascular profile in Cluster 2. Conclusion: Serum chemokine and adhesion molecule profiles may help stratify early severe SSc into biologically distinct subgroups with different pulmonary trajectories, supporting their potential utility for early risk stratification in SSc-ILD.