Complex biological patterns of soluble cytokines and CD163 in childhood necessitating age-specific reference intervals for evidence-based clinical interpretation Journal Article


Authors: Sepiashvili, L.; Alli, Z.; Bohn, M. K.; Hall, A.; Karin, A.; Murata, K.; Adeli, K.
Article Title: Complex biological patterns of soluble cytokines and CD163 in childhood necessitating age-specific reference intervals for evidence-based clinical interpretation
Abstract: 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® EllaTM 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. © 2021 The Canadian Society of Clinical Chemists
Keywords: pediatric; cytokines; reference values; multi-analyte immunoassay
Journal Title: Clinical Biochemistry
Volume: 98
ISSN: 0009-9120
Publisher: Elsevier Inc.  
Date Published: 2021-12-01
Start Page: 35
End Page: 41
Language: English
DOI: 10.1016/j.clinbiochem.2021.09.004
PUBMED: 34509468
PROVIDER: scopus
PMCID: PMC9433181
DOI/URL:
Notes: Article -- Export Date: 1 December 2021 -- Source: Scopus
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  1. Kazunori Murata
    33 Murata