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

Background: The granulocyte-macrophage-colony-stimulating factor (GM-CSF) plays an important role in surfactant homeostasis. βC is a subunit of the GM-CSF receptor (GM-CSF-R), and its activation mediates surfactant catabolism in the lung. βIT is a physiological, truncated isoform of βC and is known to act as physiological inhibitor of βC.

Objective: The aim of this study was to determine the ratio of βIT and βC in the peripheral blood of newborns and its association with the degree of respiratory failure at birth.

Methods: 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). βIT and βC expression were determined in peripheral blood cells by real-time PCR. βIT expression, defined as the ratio of βIT and βC, was correlated with the respiratory score.

Results: βIT expression was found in all 59 recruited newborns with a trend toward higher βIT in respiratory ill (score 2, 3) newborns than respiratory healthy newborns ([score 0, 1]; p = 0.066). Seriously ill newborns (score 3) had significantly higher βIT than healthy newborns ([score 0], p = 0.010). Healthy preterm infants had significantly higher βIT expression than healthy term infants (p = 0.019).

Conclusions: βIT is expressed in newborns with higher expression in respiratory ill than respiratory healthy newborns. We hypothesize that βIT may have a protective effect in postnatal pulmonary adaptation acting as a physiological inhibitor of βC and, therefore, maintaining surfactant in respiratory ill newborns.