Soluble receptor for advanced glycation end products (sRAGE) in tracheobronchial aspirate fluid and cord blood of very low birth weight infants with chorioamnionitis and funisitis

Abstract: Background: A systemic fetal inflammatory response, reflected by histological funisitis is associated with pulmonary morbidity and increased mortality after premature birth. The receptor for advanced glycation end products (RAGE) is a membrane-bound multiligand receptor with a key role in inflammation. Soluble RAGE (sRAGE) is created by alternative mRNA splicing or shedding of the receptor''s extracellular domain and can inhibit RAGE-activation. Aims: To assess the association of funisitis with airway and systemic concentrations of sRAGE in very premature infants. Methods: Forty-two ventilated infants (gestational age: 27.4±1.8weeks, birth weight: 1017±229g [mean±SD]) were studied. sRAGE concentrations were measured in tracheobronchial aspirate fluid (TAF) on days of life 1, 3, 5, 7 and 10 and in umbilical cord serum of 28 infants by ELISA. The secretory component for IgA (SC) served as reference protein in TAF. Placental tissue, membranes and umbilical cords were examined microscopically to distinguish three groups: chorioamnionitis (n =9), funisitis (n =17) and controls (n =16). Results: The funisitis group had lower sRAGE concentrations than both other groups in cord blood serum (median: 0.52ng/ml [25th–75th centile: 0.32–0.91]; control, 1.72 [1.02–2.69]; chorioamnionitis, 1.44 [0.92–1.63], p <0.01) and TAF on day 1 (290ng/ngSC [140–400]; control, 2750 [1470–28920]; chorioamnionitis, 2150 [1220–7140], p <0.01). sRAGE in TAF remained lower in the funisitis than in the chorioamnionitis group on days 3 and 10, p <0.01 respectively. Conclusions: Decreased sRAGE in airways and circulation after funisitis may contribute to an imbalance between pro- and anti-inflammatory factors priming very premature infants for pulmonary injury and increasing the risk of adverse outcome. [Copyright &y& Elsevier]