Soluble Forms and Ligands of RAGE in ALI/ARDS (SoLiRAGE).

Acute Lung Injury, Acute Respiratory Distress Syndrome, Mechanical Ventilation

Receptor for advanced glycation end products (RAGE), Soluble RAGE (sRAGE), Endogenous secretory RAGE (esRAGE), High-mobility group box-1 protein (HMGB-1), Extracellular newly-identified RAGE-binding protein (EN-RAGE or S100A12), Advanced glycation endproducts (AGEs), Pentosidine, N--carboxymethyllysine, Acute lung injury (ALI), Acute respiratory distress syndrome (ARDS), Alveolar epithelium, Mechanical ventilation, Intensive Care Unit (ICU)

RAGE, the receptor for advanced glycation end products, is a novel marker of alveolar epithelial type I cell injury. Soluble RAGE (sRAGE) is elevated in the plasma and in the pulmonary edema fluid from patients with ALI/ARDS, but one should acknowledge that the RAGE/NF-B axis is also involved in the pathophysiology of various other conditions. Few data are available about the levels of soluble forms and ligands of RAGE in the setting of ALI/ARDS. The purpose of this observational prospective study is to describe soluble forms (sRAGE, esRAGE) and ligands of RAGE (HMGB-1, S100A12, AGEs) levels in ICU patients with ALI/ARDS.

BACKGROUND: The receptor for advanced glycation end products (RAGE) is now identified as a marker of alveolar type I cell injury. RAGE is a member of the immunoglobulin superfamily that acts as a multiligand receptor and is involved in propagating inflammatory responses. While the precise function of RAGE remains unclear, the elevated levels of RAGE, and its soluble isoform sRAGE, correlate with severity of ALI/ARDS in human and animal studies, and RAGE levels could reflect impaired alveolar fluid clearance. Frequently, the biology of RAGE coincides with settings in which ligands of the receptor accumulate, especially in a proinflammatory environment. More work is needed for us to understand the mechanisms by which RAGE is regulated during ALI/ARDS, especially with regard to the expression of its soluble forms and the involvement of its potential ligands. DESIGN NARRATIVE: This observational prospective clinical study will describe and compare soluble forms (sRAGE, esRAGE) and ligands of RAGE (HMGB-1, S100A12, AGEs) levels in the alveolar edema fluid and in the plasma from ICU patients enrolled within the first 24 hours after onset of ALI/ARDS, and from patients under mechanical ventilation (control group). Edema fluid and plasma samples will be collected simultaneously on day 1, day 3 and day 6, in order to describe kinetics of evolution of soluble forms and ligands of RAGE levels. Undiluted pulmonary edema fluid samples will be collected in intubated patients only, and blood samples will be simultaneously gathered from indwelling arterial and central venous catheters. The concentrations of soluble forms (sRAGE, esRAGE) and ligands of RAGE (HMGB-1, S100A12, AGEs) will be measured in duplicate by ELISA.

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France