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Published on: November 9, 2017
Complex biological patterns of soluble cytokines and CD163 in childhood necessitating age-specific reference
Lusia Sepiashvili1, Zaman Alli2, Mary Kathryn Bohn3
1Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; SickKids Research Institute, 686 Bay Street, Toronto, ON M5G 0A4, Canada.
Insights
Accurate pediatric reference intervals (RIs) for cytokines like IL-6 and TNF-α are crucial for clinical interpretation. This study establishes age- and sex-specific RIs for inflammatory markers in children aged 1-19 years.
Area of Science:
- Pediatric immunology
- Clinical chemistry
- Biomarker research
Background:
- Cytokine measurements are vital in pediatric research and clinical practice.
- Accurate pediatric reference intervals (RIs) are lacking for interpreting cytokine results.
- This study addresses the need for age- and sex-specific RIs in children.
Purpose of the Study:
- To establish pediatric reference values for key inflammatory markers.
- To determine age- and sex-specific reference intervals (RIs) for cytokines and CD163.
- To provide data for accurate interpretation of cytokine measurements in children.
Main Methods:
- Recruited 311 healthy children and adolescents (1-19 years) for the CALIPER study.
- Utilized ProteinSimple® Ella™ platform for multi-analyte plasma measurements.
- Calculated age- and sex-specific RIs and percentile cut-offs per CLSI guidelines.
Main Results:
- Observed three distribution patterns: consistent (IL-6, IFN-γ), age-declining (CD163, TNF-α, CXCL-9, IL-10), and age-peak (IL-1β, IL-18).
- Found significant age differences for CXCL-9, IL-10, TNF-α under 8 years.
- Identified age partitions for CD163, IL-18, IL-1β, and sex differences for CD163 in specific age groups.
Conclusions:
- Pediatric cytokine profiles are complex, varying by age and sex.
- Age- and sex-specific RIs are essential for accurate clinical decision-making.
- This study provides critical reference data for pediatric cytokine testing.
Background:
Cytokine measurements to support clinical laboratory and research investigations have become increasingly common in pediatrics. However, there is a paucity of accurate pediatric reference intervals (RIs) essential to the interpretation of cytokine results. To address this gap, here, we establish age- and sex-specific pediatric reference values for clinically relevant inflammatory markers including CD163, and the cytokines IL-1β, IL-6, IL-10, IL-18, TNF-α, IFN-γ, and CXCL-9.
Methods:
Healthy children and adolescents (n = 311, 1-19 years) were recruited as part of the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) study. Multi-analyte measurements in plasma and analytical performance verification were conducted on the ProteinSimple® Ella™ automated immunoassay platform (Bio-Techne, MN, USA). Age- and sex-specific RIs were calculated based on Clinical and Laboratory Standards Institute guidelines. Additionally, 75th and 95th percentile cut-offs were determined.
Results:
Three types of reference value distributions were observed: (a) consistent levels throughout age and sex: IL-6, and IFN-γ, (b) gradual decline in concentration with age: CD163, TNF-α, CXCL-9, and IL-10, (c) significantly higher concentrations during ages 4-14 years than earlier and later ages: IL-1β and IL-18. Reference values for CXCL-9, IL-10, and TNF-α under 8 years of age differed significantly from older children. CD163, IL-18 and IL-1β required three age partitions. CD163 demonstrated significant sex differences in ages 8-13 years.
Conclusion:
The circulating profile of cytokines in children is complex and can vary by age and sex. This necessitates careful interpretation of test results based on age and/or sex specific RIs facilitating more accurate clinical decision making.
