Identification of candidate biomarkers for severe adenovirus community-acquired pneumonia by proteomic approach

Area of Science:

• Biochemistry
• Pediatrics
• Infectious Diseases

Background:

• Human adenoviruses (ADV) are a significant cause of childhood mortality globally.
• Current methods for assessing the severity of ADV-associated Community-Acquired Pneumonia (CAP) rely on clinical features, lacking rapid and accurate diagnostic biomarkers.
• Early intervention is crucial for managing severe pediatric ADV CAP.

Purpose of the Study:

• To screen for candidate biomarkers for severe pediatric ADV CAP.
• To identify differentially expressed proteins associated with ADV CAP severity.
• To evaluate the potential of identified proteins as diagnostic markers for early intervention.

Main Methods:

• Serum samples from healthy children, and patients with ADV CAP, Streptococcus pneumoniae (SP) CAP, and Respiratory Syncytial Virus (RSV) CAP were analyzed.
• iTRAQ-based mass spectrometry was used to identify differentially expressed proteins (DEPs).
• Gene Ontology, Pathway Enrichment analysis, and protein-protein interaction networks were constructed to analyze DEPs.

Main Results:

• 119 DEPs in mild ADV CAP and 148 DEPs in severe ADV CAP were identified compared to healthy controls.
• Four proteins (S100A9, S100A8, Leucine aminopeptidase III (LAP3), and Apolipoprotein A-IV (APOA4)) were validated by Western blot.
• LAP3 was significantly upregulated in severe ADV CAP compared to mild ADV CAP, SP CAP, and RSV CAP, indicating its potential as a severity marker.

Conclusions:

• Leucine aminopeptidase III (LAP3) protein is identified as a potential diagnostic biomarker for assessing the severity of ADV CAP in children.
• This discovery may facilitate earlier clinical intervention for severe pediatric ADV CAP.
• LAP3 shows promise in differentiating ADV CAP severity and in comparison to other common pediatric respiratory infections.