A Role for RAGE/TXNIP/Inflammasome Axis in Alveolar Macrophage Activation During ARDS (RIAMA): a Proof-of-concept Clinical Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- FACS analysis of RAGE-TXNIP-NLRP3 pathway in alveolar monocytes/macrophages
研究概览
简要总结
RAGE (the receptor for advanced glycation end-products) is a marker of alveolar type I cell injury and a pivotal mediator of acute inflammation and innate immunity. RAGE pathway is highly regulated; the interaction of the transmembrane receptor with its various ligands (e.g. HMGB1, S100A12) ultimately leads to NF-kB activation and RAGE upregulation itself, but precise RAGE functions and intracellular pathways remain underexplored. During ARDS, monocyte and macrophage activation could modulate alveolar inflammation and repair.
As RAGE is also expressed at the surface of monocytes/macrophages, we hypothesize that alveolar monocyte/macrophage activation may be mediated through a RAGE-TXNIP (thioredoxin interacting protein)-NLRP3/inflammasome intracellular pathway. The purpose of this observational prospective study is to compare alveolar monocyte/macrophage activation profiles (as assessed by Fluorescence-Activated Cell Sorting (FACS)) in mechanically ventilated patients with or without ARDS.
详细描述
BACKGROUND:
The receptor for advanced glycation end products (RAGE) was recently identified as a promising new 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 in various cell populations. While the precise function of RAGE remains unclear, the elevated levels of RAGE, and its soluble isoform sRAGE, correlate with severity of acute respiratory distress syndrome (ARDS) in human and animal studies.
RAGE pathway is highly regulated; the interaction of the transmembrane receptor with its various ligands (e.g. HMGB1, S100A12) ultimately leads to NF-kB activation and RAGE upregulation itself. During ARDS, monocyte and macrophage activation could modulate alveolar inflammation and repair. As RAGE is also expressed at the surface of monocytes/macrophages, we hypothesize that alveolar monocyte/macrophage activation may be mediated through a RAGE-TXNIP (thioredoxin interacting protein)-NLRP3/inflammasome intracellular pathway.
DESIGN NARRATIVE:
The purpose of this monocentric observational prospective pathophysiology study is to compare alveolar monocyte/macrophage activation profiles between patients with or without ARDS.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 95 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ICU patients without ARDS and under mechanical ventilation for less than 24 hours
- •Patients within the first 24 hours after onset of moderate to severe ARDS according to the 2012 Berlin definition (ARDS group)
排除标准
- •- Pregnancy
- •Acute exacerbation of diabetes (ketoacidosis, hyperosmolar hyperglycemic state)
- •Patient under mechanical ventilation for > 7 days
- •Dialysis-dependent chronic renal failure
- •Alzheimer's disease
- •Amyloidosis
- •Evolutive neoplastic lesion
- •Chronic pulmonary disease requiring long-term oxygen therapy or mechanical ventilation
- •Chemotherapy treatment in the last 30 days
- •Severe neutropenia (<0.5 G/l)
结局指标
主要结局
FACS analysis of RAGE-TXNIP-NLRP3 pathway in alveolar monocytes/macrophages
时间窗: at day1
FACS analysis of RAGE-TXNIP-NLRP3 pathway in alveolar monocytes/macrophages from patients within the first 24 hours after onset of ARDS (ARDS group) and from sex- and age-matched mechanically ventilated controls (control group)
次要结局
- - FACS analysis of M1 ("pro-inflammatory") and M2 ("anti-inflammatory") markers(at baseline)
- IL-1β, TXNIP, NLRP3, sRAGE, HMGB1, S100A12 measurements(at baseline)