AUTHOR=Thomson Lindsay M. , Mancuso Christopher A. , Wolfe Kelly R. , Khailova Ludmila , Niemiec Sierra , Ali Eiman , DiMaria Michael , Mitchell Max , Twite Mark , Morgan Gareth , Frank Benjamin S. , Davidson Jesse A. 

TITLE=The proteomic fingerprint in infants with single ventricle heart disease in the interstage period: evidence of chronic inflammation and widespread activation of biological networks

JOURNAL=Frontiers in Pediatrics

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2023.1308700

DOI=10.3389/fped.2023.1308700

ISSN=2296-2360

ABSTRACT=<sec><title>Introduction</title><p>Children with single ventricle heart disease (SVHD) experience significant morbidity across systems and time, with 70% of patients experiencing acute kidney injury, 33% neurodevelopmental impairment, 14% growth failure, and 5.5% of patients suffering necrotizing enterocolitis. Proteomics is a method to identify new biomarkers and mechanisms of injury in complex physiologic states.</p></sec><sec><title>Methods</title><p>Infants with SVHD in the interstage period were compared to similar-age healthy controls. Serum samples were collected, stored at −80°C, and run on a panel of 1,500 proteins in single batch analysis (Somalogic Inc., CO). Partial Least Squares-Discriminant Analysis (PLS-DA) was used to compare the proteomic profile of cases and controls and t-tests to detect differences in individual proteins (FDR &lt;0.05). Protein network analysis with functional enrichment was performed in STRING and Cytoscape.</p></sec><sec><title>Results</title><p>PLS-DA readily discriminated between SVHD cases (<italic>n</italic> = 33) and controls (<italic>n</italic> = 24) based on their proteomic pattern alone (Accuracy = 0.96, <italic>R</italic><sup>2 </sup>= 0.97, <italic>Q</italic><sup>2 </sup>= 0.80). 568 proteins differed between groups (FDR &lt;0.05). We identified 25 up-regulated functional clusters and 13 down-regulated. Active biological systems fell into six key groups: angiogenesis and cell proliferation/turnover, immune system activation and inflammation, altered metabolism, neural development, gastrointestinal system, and cardiac physiology and development.</p></sec><sec><title>Conclusions</title><p>We report a clear differentiation in the circulating proteome of patients with SVHD and healthy controls with &gt;500 circulating proteins distinguishing the groups. These proteomic data identify widespread protein dysregulation across multiple biologic systems with promising biological plausibility as drivers of SVHD morbidity.</p></sec>