Key result
Interstage single ventricle infants exhibit widespread proteomic dysregulation involving 568 proteins versus healthy controls.
Why the study?
Children with single ventricle heart disease experience significant multisystem morbidity, and proteomics may identify new biomarkers and mechanisms of injury.
Case-Control (n=57)
No
Effect estimate: Accuracy 0.96
Infants with single ventricle heart disease in the interstage period exhibit widespread proteomic dysregulation compared to healthy controls, highlighting potential new biomarkers and mechanisms of morbidity.
Proteomic differences highlight chronic inflammation in interstage SVHD; hypothesis-generating for biomarkers and requires validation before clinical use.
Introduction: 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. Methods: 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 <0.05). Protein network analysis with functional enrichment was performed in STRING and Cytoscape. Results: = 0.80). 568 proteins differed between groups (FDR <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. Conclusions: We report a clear differentiation in the circulating proteome of patients with SVHD and healthy controls with >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.
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Thomson et al. (2023) conducted a case-control in Single ventricle heart disease (SVHD) (n=57). Single ventricle heart disease (SVHD) vs. Healthy controls was evaluated on Proteomic profile discrimination between cases and controls (Accuracy 0.96). Infants with single ventricle heart disease in the interstage period exhibited a distinct circulating proteome compared to healthy controls, with 568 differentially expressed proteins (FDR <0.05) indicating widespread dysregulation across multiple biological systems.
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