Reduced endogenous secretory RAGE in blood and bronchoalveolar lavage fluid is associated with poor prognosis in idiopathic pulmonary fibrosis

BACKGROUND: The endogenous secretory receptor for advanced glycation end products (esRAGE) is a soluble isoform produced by alternative splicing of the RAGE gene. The isoform has anti-inflammatory properties due to its inhibition of the RAGE/ligand interaction and is reduced in the lung tissue of patients with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the association of esRAGE serum and bronchoalveolar lavage fluid (BALF) levels with progression of IPF. METHODS: This study included 79 IPF patients and 90 healthy controls. IPF and control serum esRAGE levels were compared, and the correlation between serum and BALF esRAGE levels was analyzed in 57 IPF patient samples. We also investigated the relationship of esRAGE serum and BALF levels with prognoses and lung function parameters in patients with IPF. RESULTS: Serum esRAGE levels in IPF patients were significantly lower than those in healthy controls (162.0 ± 102.4 ng/ml and 200.7 ± 107.3 ng/ml, p = 0.009), although the baseline characteristics of age and smoking history were not matched. Serum levels of esRAGE were correlated with BALF esRAGE levels (r(s) = 0.317). The BALF esRAGE levels were also correlated with diffusion capacity for carbon monoxide (r(s) = 0.406). A Kaplan-Meier curve analysis and univariate/multivariate Cox hazard proportion analysis revealed that lower levels of esRAGE in blood and BALF were significantly associated with poorer prognoses in patients with IPF. CONCLUSIONS: Decreased esRAGE levels in BALF and blood were associated with poor prognoses in patients with IPF. These results suggest that esRAGE could be related to the pathophysiology of IPF and serum esRAGE could be a potential prognostic marker of IPF.