Lung fluid proteome in premature infants and respiratory outcome

Ballard PL, Oses-Prieto J, Chapin C, Burlingame A, Ballard RA University of California, San Francisco, USA Email: Phil.ballard@ucsf.edu Background: Infants of extremely low gestational age are at high risk for lung disease continuing through childhood. Pathogenic mechanisms are not fully defined and there are currently no clinically useful biomarkers to assess risk. Methods: TA samples were collected at 7-28 days from intubated TOLSURF infants of <28 wk. Cell-free TA supernatants were assessed for protein composition by trypsinization, HPLC and tandem mass spectrometry/spectral analysis. Results: In TA samples from 39 infants, peptides for 809 different proteins were present in >25% of the samples. Based on RNAseq data from human foetal lung and infant plasma proteomics, ~88% of the proteins are likely of lung origin with the rest originating from plasma. In comparison of the proteomes of infants with extreme respiratory outcomes, candidate protein biomarkers of both lung and plasma origin were identified (1.2to 3.9-fold). Proteins decreased with lung disease included vitamin D-binding protein, gamma enolase, C3, and annexin A5. Notably, all 7 hemoglobin subunits detected were increased 2to 3-fold. Conclusions: Global proteomics demonstrates that lung fluid of premature infants contains a variety of proteins of both lung and plasma origin, and that some proteins are candidate biomarkers for respiratory outcome. Elevated airspace free haemoglobin and hemin, which are both prooxidants, in early postnatal life secondary to haemorrhagic edema and haemolysis may contribute to persistent lung disease by depleting nitric oxide and increasing oxidative/nitrative stress.