Krebs Von Den Lungen-6 as a biomarker for lung disease activity and diagnosis in systemic juvenile idiopathic arthritis

OBJECTIVES: Children with systemic juvenile idiopathic arthritis (sJIA) and lung disease (LD) are at increased risk of serious complications and premature mortality, making early detection and intervention critical. Krebs von den Lungen 6 (KL-6) is a blood-based biomarker for interstitial lung disease in adults; however, its role in pediatric LD is unclear. This study evaluates KL-6 as a discriminatory and disease activity biomarker for sJIA-LD. METHODS: Thirty-two patients with sJIA-LD were enrolled through the Childhood Arthritis and Research Alliance (CARRA) Registry. Comparators included sJIA patients without LD, children with primary pulmonary alveolar proteinosis (PAP), and healthy control children. RESULTS: Median KL-6 levels were significantly higher in sJIA-LD (596.3 U/mL [IQR 273.5-5,896.3]) compared to sJIA without LD (193.0 U/mL [151.0-252.0], p < 0.0001) and healthy controls (171.9 U/mL [89.7-224.3], p = 0.001), with no difference versus PAP (596.3 vs. 1429.9, p = 0.30). A cut-off of 259.5 U/mL yielded 81.3% sensitivity and 80.9% specificity for LD (AUC 0.856, p < 0.0001). At 371.5 U/mL, specificity reached 100% with 68.7% sensitivity and 100% positive predictive value. SJIA-LD features associated with higher median KL-6 levels included oxygen requirement, abnormal pulse oximeter (<90%), and abnormal chest radiographs. KL-6 strongly correlated with physician global assessment of lung disease but not with markers of systemic inflammation or macrophage activation syndrome. CONCLUSION: KL-6 is a useful biomarker for discriminating LD and evaluating disease activity in sJIA-LD. Future efforts should focus on the utility of KL-6 for monitoring disease progression, treatment response, and predicting long-term disease trajectories.