Pulmonary Aptamer Signatures in Children's Interstitial and Diffuse Lung Disease.

Rationale: Biomarker signatures are needed in children with children's interstitial and diffuse lung disease (chILD) to improve diagnostic approaches, increase our understanding of disease pathogenesis, monitor disease progression, and develop new treatment strategies. Proteomic technology using SOMAmer (Slow Off-rate Modified Aptamer) nucleic acid-based protein-binding reagents allows for biomarker discovery.
Objectives: We hypothesized that proteins and protein pathways in BAL fluid (BALF) would distinguish children with neuroendocrine cell hyperplasia of infancy (NEHI), surfactant dysfunction mutations, and other chILD diagnoses and control subjects.
Methods: BALF was collected for clinical indications and banked in patients with chILD and disease control subjects using standardized protocols over 10 years. BALF supernatant was analyzed using an aptamer assay to measure 1,129 protein levels. Protein levels were compared between groups using an ANOVA and adjusted for multiple comparisons using false discovery rate. Proteins were classified into pathways. Hierarchical clustering was used to define endotypes in the group of children with NEHI.Measurements and Main
Results: After correcting for multiple testing, children with NEHI (n = 22) had 202 aptamers that were significantly different (P < 0.05) in BALF compared with control subjects (n = 9). Children with surfactant mutation (n = 8) had 51 aptamers significantly different (P < 0.05) in BALF compared with control subjects (n = 9). Proteins associated with pulmonary fibrosis and inflammation were associated with the surfactant dysfunction group but not the NEHI group. Using hierarchical clustering analysis, two distinct NEHI endotypes were identified.Conclusions: Distinct proteins and protein pathways can be determined from BALF of children with chILD, and these hold promise to further our understanding of chILD.