RAGE expression in lung tissue of ARDS and septic patients

Abstract

Background: Several studies have indicated the involvement of receptor for advanced glycation end products (RAGE) in the pathophysiology of ARDS and its potential as biomarker, however there are scarce information on the expression profile of RAGE in lung tissue of ARDS patients. Aims: To assess the alveolar epithelium expression of membrane-bound RAGE of patients with ARDS and sepsis. Methods: Using immunohistochemistry and image analysis, we quantified membrane-bound RAGE expression in the lung epithelium of patients who died of ARDS (with or without sepsis; classified according to the Berlin definition; n=13) and sepsis (without criteria for ARDS; n=15) who had their autopsies performed at the Sao Paulo Autopsy Service (Brazil) and correlated it with clinical variables. Results: The severe ARDS patients (0.36ǂ0.02) had higher RAGE expression than the mild ARDS (0.19±0.02; p=0.001) and the septic patients (0.25±0.04; p=0.019). The septic patients had the expression of RAGE negatively correlated with hospitalization days (r=-0.667; p=0.007) and positively correlated with serum lactate levels (r=0.658; p=0.02) and hematocrit (r=0.75; p=0.012). In ARDS patients, the alveolar epithelium RAGE expression is negatively correlated with hospitalization days (r=-0.685; p=0.010) and with the PaO2/FiO2 ratio (r=-0.656; p=0.021). Conclusion: Our results show that the membrane-bound RAGE epithelium expression is higher in patients with severe ARDS than in septic patients, and it correlates with ARDS severity. These results corroborate previous studies that show that patients with severe ARDS have increased levels of soluble RAGE, reinforcing the evidence that it could be a valuable biomarker candidate.