Interleukin-40 levels serve as a treatment-sensitive marker in systemic sclerosis, not a disease activity indicator.

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by widespread fibrosis and vascular damage, with significant morbidity and mortality. Immune dysregulation, particularly involving B cells, is a central driver of SSc pathogenesis, yet specific biomarkers reflecting immune modulation by therapy are lacking. Interleukin-40 (IL-40), a cytokine primarily produced by activated B cells, has been implicated in immune regulation across various autoimmune conditions. However, its precise role and clinical utility as a circulating marker in SSc, especially in response to immunosuppressive treatments, remain poorly understood, representing a critical knowledge gap this study addresses.

This cross-sectional study measured serum Interleukin-40 (IL-40) levels using ELISA in 41 patients with Systemic sclerosis (SSc) and 29 age- and sex-matched healthy controls. SSc patients were categorized by their immunosuppressive treatment status at serum collection. Clinical features, organ involvement, and disease activity were recorded. The primary objective was to characterize circulating IL-40 levels and explore their associations with treatment exposure, disease subsets, clinical manifestations, and disease activity.