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Expression, Purification, and Antimicrobial Activity of S100A12
Published on: May 13, 2017
Plasma calprotectin as a severity biomarker in pediatric invasive Streptococcus pyogenes infections: insights from a
José Avendaño-Ortiz1, David Aguilera-Alonso2, Concepción M Rodríguez3
1Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.
Insights
Plasma calprotectin and IL-6 levels can help identify children with invasive Streptococcus pyogenes infections (iGAS) who may need intensive care. These biomarkers aid in early detection of severe pediatric iGAS cases.
Area of Science:
- Pediatric infectious diseases
- Immunology
- Biomarker discovery
Background:
- Invasive Streptococcus pyogenes infections (iGAS) pose a significant threat to children.
- Understanding the immune response in pediatric iGAS is crucial for managing disease severity.
- Current biomarkers for iGAS severity require further investigation.
Purpose of the Study:
- To characterize the immune signature of pediatric iGAS infections.
- To identify host biomarkers associated with iGAS disease severity.
- To evaluate the potential of specific biomarkers in predicting the need for pediatric intensive-care unit (PICU) admission.
Main Methods:
- Plasma samples from a Spanish pediatric cohort (n=32) with iGAS, S. pyogenes acute tonsillitis, and healthy controls were analyzed.
- A panel of 56 soluble immune markers, including cytokines and vascular markers, were quantified.
- Patients were stratified based on PICU admission, and receiver operating characteristic (ROC) curve analysis was performed.
Main Results:
- Children with S. pyogenes infection showed upregulated vascular inflammation markers.
- Patients requiring PICU admission had elevated levels of CXCL10, IL-6, IL-10, IL-17A, sCD14, sCD40L, calprotectin, angiopoietin 2, and HGF.
- Calprotectin and IL-6 demonstrated high accuracy (AUC > 0.90) in predicting PICU admission, with calprotectin independently associated with PICU need.
Conclusions:
- Pediatric iGAS involves a complex immune landscape with both vascular and immune mediators.
- Plasma calprotectin is a promising biomarker for assessing iGAS severity in children.
- Early identification of high-risk pediatric iGAS patients may be improved using calprotectin levels.
Purpose:
To characterize the immune signature of pediatric invasive Streptococcus pyogenes infections (iGAS) and identify host biomarkers associated with disease severity.
Methods:
Plasma samples (n = 32) were collected during an iGAS outbreak from a multicentric Spanish pediatric cohort, including patients with iGAS (n = 19), S. pyogenes acute tonsillitis (n = 3), and healthy children/controls (n = 10). Patients were monitored and stratified based on the need of pediatric intensive-care unit (PICU). A panel of 56 soluble markers -including cytokines, chemokines, immune-checkpoints, antimicrobial peptides, growth factors, and vascular inflammation, myeloid and thrombosis markers- were quantified in plasma.
Results:
Regardless of disease severity, children with S. pyogenes infection exhibited a systemic inflammatory profile characterized by an upregulation of vascular inflammation markers. Patients with iGAS requiring PICU admission were mostly infected by emm1 S. pyogenes harboring speA and speJ genes and exhibited an immune profile characterized by alterations in CXCL10, IL-6, IL-10, IL-17A, sCD14, sCD40L, calprotectin, angiopoietin 2 and HGF. Area under the ROC curve analysis revealed that calprotectin and IL-6 exhibited the best classificatory performance for PICU admission (p < 0.01; AUC = 0.90 and AUC = 0.91, respectively), with an optimal Youden cut-off for calprotectin of 2753 ng/mL. A logistic regression model integrating both biomarkers and routine clinical parameters revealed an independent association between calprotectin levels and PICU admission.
Conclusion:
Pediatric iGAS is characterized by a complex immune landscape involving a combination of vascular and immune response mediators. Plasma calprotectin levels emerge as a promising severity biomarker, potentially aiding in the early identification of high-risk patients.

