Anti-Ro52 Seropositive Interstitial Lung Disease Is Associated With a Higher Risk of Disease Progression and Mortality.

Background: Identifying biomarkers is vital for interstitial lung disease (ILD) management and prognostication. Although anti-Ro52 antibodies frequently are detected in autoimmune diseases, their significance in ILD remains unclear.

Research question: What is the prognostic significance of anti-Ro52 antibody positivity in patients with ILD?

Study design and methods: This retrospective cohort study used an ILD registry of patients seen at an academic tertiary hospital's ILD clinic between 2015 and 2024. All patients with a diagnosis of ILD and tested for anti-Ro52 antibody status were divided into anti-Ro52 positive and negative groups. The primary outcome was ILD progression or all-cause death. ILD progression was defined as any of the following: hospitalization because of ILD, absolute decline in FVC of ≥ 10% predicted from baseline, or lung transplantation. The Kaplan-Meier method and Cox proportional hazards regression model were used for survival analysis.

Results: Of 1,026 patients tested for the anti-Ro52 antibody (median age, 70 years; 52% male), 154 patients (15%) showed positive anti-Ro52 results. Underlying ILD subtypes were as follows: interstitial pneumonia with autoimmune features (n = 489 [48%]), connective tissue disease (CTD)-associated ILD (n = 132 [13%]), idiopathic pulmonary fibrosis (n = 103 [10%]), hypersensitivity pneumonitis (n = 61 [6%]), and other idiopathic ILD (n = 241 [24%]). The anti-Ro52-positive group was younger (median age, 67 years vs 70 years), was more likely to have CTD (28% vs 10%), and more frequently showed copositive results for myositis-specific antibody (29% vs 16%). After a median follow-up of 25.6 months, patients with positive anti-Ro52 findings showed a higher risk of ILD progression or death (hazard ratio, 2.10; 95% CI, 1.61-2.73; P < .001) and showed a higher risk of lung transplantation or death (hazard ratio, 1.61; 95% CI, 1.11-2.35; P = .014) on multivariable analysis.

Interpretation: Anti-Ro52-seropositive ILD is associated with significantly worse progression-free and transplant-free survival and may inform disease prognostication and monitoring.