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Published on: June 28, 2018
Defining age-specific reference intervals for biomarkers distinguishing bacterial from viral infection in paediatrics
Clare Mills1, Damaris Condy1, Beth Cartmill1
1Wellcome-Wolfson Institute For Experimental Medicine, Queen's University Belfast, 97 Lisburn Rd, Belfast BT9 7BL, United Kingdom.
Insights
This study establishes reference intervals for novel infection biomarkers (IP-10, LCN2, TRAIL) in healthy children. These findings aid in differentiating bacterial from viral infections, improving pediatric care and antimicrobial stewardship.
Area of Science:
- Pediatric Infectious Diseases
- Immunology
- Biomarker Discovery
Background:
- Differentiating bacterial from viral infections in children is clinically challenging.
- Novel host immune biomarkers can aid in diagnosing infection aetiology and guiding antibiotic use.
- Limited data exists on age and sex-specific correlations and reference intervals for novel infection biomarkers in healthy children.
Purpose of the Study:
- To determine plasma levels and establish reference intervals for three novel biomarkers (IP-10, LCN2, TRAIL) in healthy children aged 2-16 years.
- To investigate age and sex-specific associations with these biomarker levels.
- To provide data supporting the use of these biomarkers in differentiating infection aetiology in pediatric populations.
Main Methods:
- Quantification of Interferon-Gamma Inducible Protein 10 kDa (IP-10), Lipocalin-2 (LCN2), and TNF-Related Apoptosis-Inducing Ligand (TRAIL) in 199 healthy pediatric plasma samples.
- Determination of 2.5th and 97.5th percentile reference intervals for each biomarker.
- Analysis of correlations between biomarker levels, sex, and age.
Main Results:
- Established reference intervals: IP-10 (36.7-168.1 pg/ml), LCN2 (14.2-123.3 ng/ml), TRAIL (57.4-71.4 pg/ml) for ages 2-16 years.
- No significant association found between biomarker levels and sex.
- TRAIL showed a weak negative correlation with age; LCN2 showed a positive correlation with age. IP-10 showed no age association.
Conclusions:
- Provides essential age-appropriate reference intervals for IP-10, LCN2, and TRAIL in healthy children.
- Findings support the potential of these biomarkers to aid in differentiating infection types in children.
- This data can enhance future research, clinical decision-making, pediatric patient outcomes, and antimicrobial stewardship.
Abstract:
Differentiating bacterial from viral infections in children is a common clinical challenge. Novel host immune biomarkers have the potential to aid thediagnosis of infection aetiology and identify children who require antibiotics. Data on novel infection biomarkers gender and age-specific correlations, and reference intervals in healthy paediatrics is lacking. This study reports the plasma levels of three novel biomarkers that can aid in the differentiation of bacterial and viral infection in a healthy group of paediatrics. The levels of (Interferon-Gamma Inducible Protein 10 kDa (IP-10), Lipocalin-2 (LCN2) and TNF-Related Apoptosis-Inducing Ligand (TRAIL) were quantified in 199 plasma samples from healthy paediatrics aged 2 to 16 years old from across the UK. Reference intervals (2.5th and 97.5th) were determined, and biomarker levels were examined for sex and age associations. Reference intervals for IP-10, LCN2 and TRAIL for ages 2-16 years were 36.7-168.1 pg/ml, 14.2-123.3 ng/ml, 57.4-71.4 pg/ml respectively. No biomarker showed an association with sex and IP-10 did not show any association with age. TRAIL levels had a weak continuous negative correlation with age and LCN2 levels had a continuous positive correlation with age. Specific cut-offs for LCN2 in two age categories were identified, while TRAIL did not require age partitions. This study provides age-appropriate reference intervals for three biomarkers of infection in healthy children. These findings have the potential to improve the impact of future research on these biomarkers, the accuracy of clinical decision-making in children with infection, paediatric patient care and outcomes, and antimicrobial stewardship.
