Prognostic Role of Interferon‐λ3 in Anti–Melanoma Differentiation–Associated Gene 5–Positive Dermatomyositis‐Associated Interstitial Lung Disease

Objective Interferon‐λ3 (IFNλ3) is a cytokine with antiviral functions on barrier surfaces, and it is associated with disease activity in autoimmune diseases. This study assessed the clinical significance of serum IFNλ3 levels in polymyositis/dermatomyositis (PM/DM)–associated interstitial lung disease (ILD). Methods We measured serum IFNλ3 levels in 221 patients with PM/DM‐ILD (155 in the derivation cohort, 66 in the validation cohort) and 38 controls. We evaluated factors associated with mortality risk among 79 patients with anti‐melanoma differentiation–associated gene 5 (MDA5) antibody–positive DM‐ILD. Results Serum IFNλ3 levels at diagnosis were significantly higher in patients with PM/DM‐ILD than in healthy controls. Remarkably, serum IFNλ3 levels were specifically increased in patients with anti‐MDA5 antibody–positive DM‐ILD in both the derivation and validation cohorts. In anti‐MDA5 antibody–positive DM‐ILD, patients with high IFNλ3 levels (>120 pg/mL) had significantly lower survival rates than those with low IFNλ3 levels (≤120 pg/mL). A multivariate analysis revealed that high IFNλ3 levels, as well as old age and low Pa o 2 , were significantly associated with poor prognoses in patients with anti‐MDA5 antibody–positive DM‐ILD. In a classification analysis of patients with anti‐MDA5 antibody–positive DM‐ILD based on age, IFNλ3 level, and Pa o 2 , patients with old age (>53 years), high IFNλ3 levels (>120 pg/mL), and low Pa o 2 (<75 mm Hg) had the worst survival. In lung pathologic analyses, IFNλ3‐positive staining was observed in macrophages, airway epithelial cells, the pleural region, and intrapulmonary veins in patients with anti‐MDA5 antibody–positive DM‐ILD. Conclusion Serum IFNλ3 is a promising biomarker for identifying patients at high risk of poor outcomes in anti‐MDA5 antibody–positive DM‐ILD.