Plasma interferon predicts pulmonary hypertension severity and outcome

Zhanping Liang¹Yun Li¹Shuying Jia²Yuyan Liu²Jie Zhu^1*Jinling Li^2*Fei Li^3*Xiaohuan Xia⁴

• ¹Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University, Shanghai, China
• ²Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
• ³Department of Radiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
• ⁴Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University, Shanghai, China

Pulmonary hypertension (PH) is a complex and progressive disease characterized by elevated pulmonary vascular resistance. Inflammation plays an important role in the pathogenesis of PH. Interferons (IFNs) are key immune cytokines that regulate cellular responses to various stimuli. This study aimed to investigate the association between IFN levels and the risk and prognosis of PH. A cohort of 875 PH patients and 182 matched controls were included. Both IFN-α and IFN-γ levels were significantly elevated in PH patients compared with controls (P < 0.05 for both), with IFN-α showing stronger predictive value across multiple PH subgroups (P < 0.05 for all), particularly in patients with Group 4 PH and idiopathic pulmonary arterial hypertension (IPAH). In Cox regression models, IFN-α was significantly associated with lower survival in PH patients (HR: 1.120, 95% CI: 1.001-1.253, P = 0.048). Kaplan-Meier analysis demonstrated that patients with IFN-α > 2.131 pg/mL had significantly lower 5-year cumulative survival rate of 60.1%, compared with 81.2% for those with IFN-α ≤ 2.131 pg/mL (Log Rank P < 0.001). A prognostic model combining IFN-α with traditional clinical markers, such as WHO-FC, 6-MWD, and NT-proBNP, improved predictive accuracy, with IFN-α contributing additional clinical net benefit in risk stratification. These findings suggest that plasma IFN-α may serve as a valuable biomarker for both predicting PH risk and assessing prognosis.