Stratifin as a Novel Diagnostic Biomarker in Serum for Diffuse Alveolar Damage

Among the various histopathological patterns of drug-induced interstitial lung disease (DILD), diffuse alveolar damage (DAD) is associated with poor prognosis. However, there is no reliable biomarker for its accurate diagnosis. Here, we show stratifin/14-3-3σ (SFN) as a biomarker candidate found in a proteomic analysis. The study included two independent cohorts and controls (n = 432 samples). SFN was specifically elevated in DILD patients with DAD, and was superior to the known biomarkers, KL-6 and SP-D, in discrimination of DILD patients with DAD from patients with other DILD patterns or other lung diseases, including bacterial pneumonia. SFN was also increased in serum from patients with idiopathic DAD, and in lung tissues and bronchoalveolar lavage fluid of patients with DAD. In vitro analysis using the A549 cell line suggested that extracellular release of SFN occurred via p53 activation. We conclude that serum SFN is a promising biomarker for DAD diagnosis.