Role of serum biomarkers KL-6, SP-D and CCL-18 in assessing interstitial lung disease in systemic sclerosis: A prospective observational study from India

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibrosis of the skin and internal organs, with interstitial lung disease (ILD) affecting over 50% of patients. Early detection and monitoring of SSc-ILD are essential for timely intervention. OBJECTIVES: To evaluate the utility of serum biomarkers Krebs von den Lungen 6 (KL-6), C-C motif chemokine ligand 18 (CCL-18) and surfactant protein D (SP-D) in assessing ILD in Indian patients with SSc. METHODS: In this prospective observational study, 76 patients with SSc were evaluated for ILD using high-resolution computed tomography (HRCT), pulmonary function tests (PFTs) and serum biomarker levels. Correlations between biomarker levels and clinical, radiological and functional parameters were assessed. RESULTS: Serum KL-6 levels showed a significant negative correlation with forced vital capacity (FVC) ( r = -0.58, P = 0.01) and were significantly elevated in patients with progressive ILD ( P < 0.0001). SP-D levels correlated significantly with HRCT scores ( r = 0.42, P = 0.04), diffusing capacity of carbon monoxide ( r = -0.528, P = 0.017) and modified Rodnan Skin Score (mRSS) ( r = 0.42, P = 0.02). CCL-18 levels demonstrated a strong positive correlation with mRSS ( r = 0.72, P = 0.016). KL-6 and CCL-18 levels were higher in patients with diffuse cutaneous SSc. SP-D levels were significantly elevated in SSc patients with ILD compared to those without ( P = 0.04). CONCLUSION: KL-6 and SP-D are promising tools for monitoring disease progression and guiding treatment in SSc-ILD, with KL-6 reflecting early alveolar inflammation and SP-D indicating the extent of alveolar injury.