Prognostic role of interferon‐lambda 3 in anti‐MDA5–positive dermatomyositis‐associated ILD

Abstract

ObjectiveInterferon‐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).MethodsWe 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.Results: 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.ConclusionSerum 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.