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


BACKGROUND
clinicaltrials.gov Identifier: NCT01270295.
CHU Clermont-Ferrand, Intensive Care Unit, Department of Anesthesiology, Critical Care and Perioperative Medicine, Estaing Hospital, Clermont-Ferrand, France; Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Matthieu
M
Jabaudon
CHU Clermont-Ferrand, Intensive Care Unit, Department of Anesthesiology, Critical Care and Perioperative Medicine, Estaing Hospital, Clermont-Ferrand, France; Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Raiko
R
Blondonnet
Clermont Université, Université d'Auvergne, Clermont-Ferrand, France; CHU Clermont-Ferrand, Department of Medical Biochemistry and Molecular Biology, Estaing University Hospital, Clermont-Ferrand, France.
Laurence
L
Roszyk
CHU Clermont-Ferrand, Department of Clinical Research and Innovation (DRCI), Clermont-Ferrand, France.
Bruno
B
Pereira
CHU Clermont-Ferrand, Intensive Care Unit, Department of Anesthesiology, Critical Care and Perioperative Medicine, Estaing Hospital, Clermont-Ferrand, France.
Renaud
R
Guérin
CHU Clermont-Ferrand, Intensive Care Unit, Department of Anesthesiology, Critical Care and Perioperative Medicine, Estaing Hospital, Clermont-Ferrand, France; Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Sébastien
S
Perbet
CHU Clermont-Ferrand, Intensive Care Unit, Department of Anesthesiology, Critical Care and Perioperative Medicine, Estaing Hospital, Clermont-Ferrand, France.
Sophie
S
Cayot
Clermont Université, Université d'Auvergne, Clermont-Ferrand, France; CHU Clermont-Ferrand, Department of Medical Biochemistry and Molecular Biology, Estaing University Hospital, Clermont-Ferrand, France.
Damien
D
Bouvier
Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Loic
L
Blanchon
Clermont Université, Université d'Auvergne, Clermont-Ferrand, France; CHU Clermont-Ferrand, Department of Medical Biochemistry and Molecular Biology, Estaing University Hospital, Clermont-Ferrand, France.
Vincent
V
Sapin
CHU Clermont-Ferrand, Intensive Care Unit, Department of Anesthesiology, Critical Care and Perioperative Medicine, Estaing Hospital, Clermont-Ferrand, France; Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.
Jean-Michel
JM
Constantin
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017127:Glycation End Products, Advanced / Q000097:blood; D024243:HMGB1 Protein / Q000097:blood; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood; D012128:Respiratory Distress Syndrome / Q000097:blood; D000067616:S100A12 Protein / Q000097:blood; D012720:Severity of Illness Index; D013997:Time Factors
C000593871:AGER protein, human; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D000067759:Receptor for Advanced Glycation End Products; D000067616:S100A12 Protein; C090441:S100A12 protein, human