Surfactant protein B proforms as potential new biomarkers for idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease (ILD) with poor prognosis. Serum biomarkers for early diagnosis, differential diagnostic separation from other ILD, and for predicting the prognosis and individual course are urgently needed. Since surfactant alterations and alveolar type II cell (AECII) apoptosis have been implicated in the pathogenesis of IPF, we tested whether the AEC-II derived precursor of surfactant protein B (ProSP-B) and the processing intermediate C-ProSP-B might serve as new serum biomarkers for IPF. We collected serum samples from 25 IPF patients. As controls, we analyzed serum samples from patients with ARDS, pneumonia, different cardiac diseases, and healthy controls. ProSP-B and C-ProSP-B levels were measured using an electro-chemiluminescence immunoassay with mouse monoclonal anti-ProSP-B antibodies. We found elevated serum levels for SP-B proforms in pulmonary disease cohorts (IPF, ARDS, Pneumonia), whereas in cardiac diseases no significant changes were found. Highest serum concentrations were found for IPF patients (ProSP-B: mean/median: 830.4/749 ng/ml and C-ProSP-B: mean/median: 2789.2/2589 ng/ml). Controls ranged at 83.8/31.8 ng/ml(mean/median, ProSP-B) and 184.8/52.2 ng/ml (mean/median, C-ProSP-B). These results could be validated in a larger prospectively collected IPF-cohort. Serum levels for ProSP-B forms were associated with disease severity, but did not change in a short term follow up. ProSP-B and C-ProSP-B may be clinically informative as diagnostic markers of IPF. Further studies are needed to establish the clinical potential of SP-B proforms as useful biomarkers and to evaluate their prognostic value.