The presence of anti-Ro52/SSA antibodies may predict concomitant pulmonary hypertension and poorer survival in patients with connective tissue disease-associated interstitial lung disease.

OBJECTIVE

Although pulmonary hypertension (PH) and interstitial lung disease (ILD) are major contributors to mortality in patients with connective tissue disease (CTD), data on concomitant PH specifically in those with CTD-associated ILD (CTD-ILD) remain limited. We aimed to identify predictors for PH development in CTD-ILD patients, and assess their impact on survival in this population.

METHOD: This retrospective observational study included 224 patients with CTD-ILD, confirmed through multidisciplinary discussion, including patients with inflammatory myopathy-associated ILD (IIM-ILD, n = 88), systemic sclerosis-associated ILD (SSc-ILD, n = 57), rheumatoid arthritis-associated ILD (RA-ILD, n = 55), and primary Sjögren's syndrome-associated ILD (pSS-ILD, n = 24). PH was diagnosed using right heart catheterization (RHC) or, in patients unable to undergo RHC, by transthoracic echocardiography. Autoantibodies related to IIM and SSc were assessed using Euroimmun immunoblot assays.

RESULTS

Among CTD-ILD patients, 28 (12.5%) had concomitant PH: SSc-ILD (21.1%), IIM-ILD (13.6%), RA-ILD (5.5%), and pSS-ILD (4.2%). Multivariate regression analysis revealed CTD duration, exertional dyspnea, nonspecific interstitial pneumonitis in HRCT, ANA-speckled pattern, anti-Ro52/SSA positivity, and anti-fibrotic agents were significant predictors of concomitant PH in overall CTD-ILD patients (all p < 0.05), and only anti-Ro52/SSA positivity is still a significant predictor in SSc-ILD/IIM-ILD subtypes. Anti-Ro52/SSA antibody positivity could predict PH emergence with AUC 0.64, specificity 75.4%, accuracy 72.3%, and negative predictive value 91.3% in CTD-ILD patients. Furthermore, CTD-ILD patients with PH and anti-Ro52/SSA positivity had higher mortality rates and shorter survival than those without PH or these autoantibodies.

CONCLUSION

Anti-Ro52/SSA antibody positivity may serve as a promising predictor of PH development and poorer survival in patients with CTD-ILD. Key Points • Pulmonary hypertension (PH) was identified in 12.5% of patients with CTD-ILD, with the highest prevalence in systemic sclerosis-ILD and inflammatory myopathy-ILD. • Anti-Ro52/SSA antibody positivity was independently associated with concomitant PH in CTD-ILD and remained significant in the SSc-ILD/IIM-ILD subgroup. • PH and anti-Ro52/SSA positivity were each associated with worse survival in CTD-ILD, supporting a potential role for anti-Ro52/SSA in risk stratification.