Soluble Forms and Ligands of the Receptor for Advanced Glycation End-Products in Patients with Acute Respiratory Distress Syndrome: An Observational Prospective Study

PLoS One. 2015 Aug 14;10(8):e0135857. doi: 10.1371/journal.pone.0135857. eCollection 2015.


Background: The main soluble form of the receptor for advanced glycation end-products (sRAGE) is elevated during acute respiratory distress syndrome (ARDS). However other RAGE isoforms and multiple ligands have been poorly reported in the clinical setting, and their respective contribution to RAGE activation during ARDS remains unclear. Our goal was therefore to describe main RAGE isoforms and ligands levels during ARDS.

Methods: 30 ARDS patients and 30 mechanically ventilated controls were prospectively included in this monocenter observational study. Arterial, superior vena cava and alveolar fluid levels of sRAGE, endogenous-secretory RAGE (esRAGE), high mobility group box-1 protein (HMGB1), S100A12 and advanced glycation end-products (AGEs) were measured in duplicate ELISA on day 0, day 3 and day 6. In patients with ARDS, baseline lung morphology was assessed with computed tomography.

Results: ARDS patients had higher arterial, central venous and alveolar levels of sRAGE, HMGB1 and S100A12, but lower levels of esRAGE and AGEs, than controls. Baseline arterial sRAGE, HMGB1 and S100A12 were correlated with nonfocal ARDS (AUC 0.79, 0.65 and 0.63, respectively). Baseline arterial sRAGE, esRAGE, S100A12 and AGEs were associated with severity as assessed by PaO2/FiO2.

Conclusions: This is the first kinetics study of levels of RAGE main isoforms and ligands during ARDS. Elevated sRAGE, HMGB1 and S100A12, with decreased esRAGE and AGEs, were found to distinguish patients with ARDS from those without. Our findings should prompt future studies aimed at elucidating RAGE/HMGB1/S100A12 axis involvement in ARDS.

Trial registration: Identifier: NCT01270295.

Publication types

  • Clinical Trial
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Female
  • Glycation End Products, Advanced / blood*
  • HMGB1 Protein / blood*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptor for Advanced Glycation End Products / blood*
  • Respiratory Distress Syndrome / blood*
  • S100A12 Protein / blood*
  • Severity of Illness Index
  • Time Factors


  • AGER protein, human
  • Glycation End Products, Advanced
  • HMGB1 Protein
  • HMGB1 protein, human
  • Receptor for Advanced Glycation End Products
  • S100A12 Protein
  • S100A12 protein, human

Associated data


Grants and funding

This work was supported by grants from Clermont-Ferrand University Hospital (“Appel d’Offre Interne” 2010, CHU Clermont-Ferrand)(Dr Jabaudon), the Auvergne Regional Council (“Programme Nouveau Chercheur de la Région Auvergne” 2013)(Pr Constantin), the Agence Nationale de la Recherche and the Direction Générale de l’Offre de Soins (“Programme de Recherche Translationnelle en Santé” ANR-13-PRTS-0010)(Dr Jabaudon). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.