The Truncated Splice Variant of the Granulocyte-Macrophage-Colony-Stimulating Factor Receptor β- Chain in Peripheral Blood Serves as Severity Biomarker of Respiratory Failure in Newborns

Abstract

<b><i>Background:</i></b> The granulocyte-macrophage-colony-stimulating factor (GM-CSF) plays an important role in surfactant homeostasis. β_C is a subunit of the GM-CSF receptor (GM-CSF-R), and its activation mediates surfactant catabolism in the lung. β_IT is a physiological, truncated isoform of β_C and is known to act as physiological inhibitor of β_C. <b><i>Objective:</i></b> The aim of this study was to determine the ratio of β_IT and β_C in the peripheral blood of newborns and its association with the degree of respiratory failure at birth. <b><i>Methods:</i></b> We conducted a prospective cohort study in newborns with various degrees of respiratory impairment at birth. Respiratory status was assessed by a score ranging from no respiratory impairment (0) to invasive respiratory support (3). β_IT and β_C expression were determined in peripheral blood cells by real-time PCR. β_IT expression, defined as the ratio of β_IT and β_C, was correlated with the respiratory score. <b><i>Results:</i></b> β_IT expression was found in all 59 recruited newborns with a trend toward higher β_IT in respiratory ill (score 2, 3) newborns than respiratory healthy newborns ([score 0, 1]; <i>p</i> = 0.066). Seriously ill newborns (score 3) had significantly higher β_IT than healthy newborns ([score 0], <i>p</i> = 0.010). Healthy preterm infants had significantly higher β_IT expression than healthy term infants (<i>p</i> = 0.019). <b><i>Conclusions:</i></b> β_IT is expressed in newborns with higher expression in respiratory ill than respiratory healthy newborns. We hypothesize that β_IT may have a protective effect in postnatal pulmonary adaptation acting as a physiological inhibitor of β_C and, therefore, maintaining surfactant in respiratory ill newborns.