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

Interferon-lambda 3 (IFN-λ3) 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 IFN-λ3 levels in polymyositis (PM)/dermatomyositis (DM)-associated interstitial lung disease (ILD).We measured serum IFN-λ3 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.Serum IFN-λ3 levels at diagnosis were significantly higher in patients with PM/DM-ILD than in healthy controls. Remarkably, serum IFN-λ3 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 IFN-λ3 levels (>120 pg/mL) had significantly lower survival rates than those with low IFN-λ3 levels (≤120 pg/mL). Multivariate analysis revealed that high IFN-λ3 levels, as well as old age and low PaO2 , 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, IFN-λ3, and PaO2 , patients with old age (>53 years), high IFN-λ3 levels (>120 pg/mL), and low PaO2 (<75 Torr) had the worst survival. In lung pathological analyses, IFN-λ3-positive staining was observed in macrophages, airway epithelial cells, the pleural region and intrapulmonary veins in anti-MDA5 antibody-positive DM-ILD.Serum IFN-λ3 is a promising biomarker for identifying patients at high risk of poor outcomes in anti-MDA5 antibody-positive DM-ILD. This article is protected by copyright. All rights reserved.