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

Matthieu Jabaudon, Raiko Blondonnet, Laurence Roszyk, Bruno Pereira, Renaud Guérin, Sébastien Perbet, Sophie Cayot, Damien Bouvier, Loic Blanchon, Vincent Sapin, Jean-Michel Constantin, Matthieu Jabaudon, Raiko Blondonnet, Laurence Roszyk, Bruno Pereira, Renaud Guérin, Sébastien Perbet, Sophie Cayot, Damien Bouvier, Loic Blanchon, Vincent Sapin, Jean-Michel Constantin

Abstract

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: clinicaltrials.gov Identifier: NCT01270295.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Log-transformed arterial, central venous and…
Fig 1. Log-transformed arterial, central venous and alveolar levels of sRAGE (in pg/ml), esRAGE (in ng/ml), HMGB1 (in ng/ml), S100A12 (in pg/ml) and AGEs (in μg/ml) in patients with ARDS (black bars) and controls over time (grey bars).
D0H0: inclusion; D0H4: 4 hours after inclusion; D3: day 3; D6: day 6). Values are reported as means±standard deviations. *P

Fig 2. Receiver-operating characteristic curves of baseline…

Fig 2. Receiver-operating characteristic curves of baseline arterial levels of sRAGE, esRAGE, HMGB1, S100A12 and…

Fig 2. Receiver-operating characteristic curves of baseline arterial levels of sRAGE, esRAGE, HMGB1, S100A12 and esRAGE in differentiating between the presence and absence of ARDS on day 0.

Fig 3. Receiver-operating characteristic curves of baseline…

Fig 3. Receiver-operating characteristic curves of baseline arterial levels of sRAGE, esRAGE, HMGB1, S100A12 and…

Fig 3. Receiver-operating characteristic curves of baseline arterial levels of sRAGE, esRAGE, HMGB1, S100A12 and esRAGE in differentiating between the presence and absence of nonfocal loss-of-aeration in computed tomography scan morphology studies on day 0 in patients with acute respiratory distress syndrome.

Fig 4. Receiver-operating characteristic curves of the…

Fig 4. Receiver-operating characteristic curves of the combination of baseline arterial sRAGE, esRAGE, HMGB1, S100A12…

Fig 4. Receiver-operating characteristic curves of the combination of baseline arterial sRAGE, esRAGE, HMGB1, S100A12 and esRAGE in differentiating between the presence and absence of nonfocal loss-of-aeration in computed tomography scan morphology studies on day 0 in patients with acute respiratory distress syndrome.
Fig 2. Receiver-operating characteristic curves of baseline…
Fig 2. Receiver-operating characteristic curves of baseline arterial levels of sRAGE, esRAGE, HMGB1, S100A12 and esRAGE in differentiating between the presence and absence of ARDS on day 0.
Fig 3. Receiver-operating characteristic curves of baseline…
Fig 3. Receiver-operating characteristic curves of baseline arterial levels of sRAGE, esRAGE, HMGB1, S100A12 and esRAGE in differentiating between the presence and absence of nonfocal loss-of-aeration in computed tomography scan morphology studies on day 0 in patients with acute respiratory distress syndrome.
Fig 4. Receiver-operating characteristic curves of the…
Fig 4. Receiver-operating characteristic curves of the combination of baseline arterial sRAGE, esRAGE, HMGB1, S100A12 and esRAGE in differentiating between the presence and absence of nonfocal loss-of-aeration in computed tomography scan morphology studies on day 0 in patients with acute respiratory distress syndrome.

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