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. 2019 Sep 14;20(1):33.
doi: 10.1186/s12865-019-0313-0.

Biological variation of immunological blood biomarkers in healthy individuals and quality goals for biomarker tests

Najib Aziz  1 , Roger Detels  2   3 , Joshua J Quint  2 , David Gjertson  4 , Timothy Ryner  2 , Anthony W Butch  5
Affiliations

Biological variation of immunological blood biomarkers in healthy individuals and quality goals for biomarker tests

Najib Aziz et al. BMC Immunol. .

Abstract

Background: Cytokines, chemokines, adipocytokines, soluble cell receptors, and immune activation markers play an important role in immune responsiveness and can provide prognostic value since they reflect underlying conditions and disease states. This study was undertaken to investigate the components of biological variation for various laboratory tests of blood immunological biomarkers.

Results: Estimates of intra-individual coefficient of variation (CVI) and inter-individual coefficient of variation (CVG) were examined for blood immunological biomarkers. Biomarkers with CVI < 10% for both genders were CD3, CD4, and CD8 T-cells, serum levels of soluble cluster of differentiation 14 (sCD14), sCD163, and soluble glycoprotein 130 (sgp130). The CVI for serum levels of adiponectin, interleukin-1 receptor antagonist (IL-1Ra), macrophage inflammatory protein 1 beta (MIP-1β), soluble CD40 Ligand (sCD40L), soluble interleukin-2 receptor alpha (sIL-2Rα), soluble interleukin-6 receptor (sIL-6R), soluble tumor necrosis factor receptor II (sTNF-RII), and tumor necrosis factor alpha (TNF-α) were between 11 and 20%. Biomarkers with CVG < 20% were CD3 T-cell, and serum concentrations of sCD14, sCD40L, and sgp130. The biomarkers with CVG > 40% were adiponectin, IL-1ra, leptin, MIP-1β, sCD163, and sIL-2Rα.

Conclusion: The biological variations of biomarkers have important monitoring value for longitudinal investigation and are essential for quality specification of tests that are performed in the laboratory. The CVI was relatively small while CVG was comparatively large and mean values of each biomarker vary between subjects. The individuality of biomarkers significantly influences reference interval values. A majority of the biomarkers in this study had strong individuality and the result of each biomarker should be cautiously interpreted if using established reference interval values. Comparison of a patient's test result with previous ones may be more useful than the usage of conventional reference values.

Keywords: Chemokine; Cytokines; Immune activation; Interleukin; Soluble markers.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Mean (filled circle) and absolute range (error bar) for each subject (n=12) over six weeks, for serum level of IL-1β (a), IL-6 (b), IFN-γ (c), IL-1Ra (d), TNF-α (e), IL-8 (f), MIP-1β (g), RANTES (h), and sCD14 (i)
Fig. 2
Fig. 2
Mean (fialled circle) and absolute range (error bar) for each subject (n=12) over six weeks, for serum level of sCD40L (a), sCD163 (b), sIL-6R (c), sIL-2Rα (d), sTNF-RII (e), sgp130 (f), Adiponectin (g), Leptin (h), and Neopterin (i)
Fig. 3
Fig. 3
Mean (filled circle) and percentage range (error bar) for each subject (n=12) over six weeks, for helper T-cell (a), Cytotoxic T-cell (b), B-cell (c), and NK cell (d)
See this image and copyright information in PMC

References

    1. Edlefsen KL, Martinez-Maza O, Madeleine MM, Magpantay L, Mirick DK, Kopecky KJ, La Croix AZ, De Roos AJ. Cytokines in serum in relation to future non-Hodgkin lymphoma risk: evidence for associations by histologic subtype. Int J Cancer. 2014;135(4):913–922. doi: 10.1002/ijc.28724. - DOI - PubMed
    1. Fahey J. Cytokines, plasma immune activation markers, and clinically relevant surrogate markers in human immunodeficiency virus infection. Clin Diagn Lab Immunol. 1998;5(5):597–603. - PMC - PubMed
    1. French MA, Cozzi-Lepri A, Arduino RC, Johnson M, Achhra AC, Landay A. Plasma levels of cytokines and chemokines and the risk of mortality in HIV-infected individuals: a case-control analysis nested in a large clinical trial. AIDS. 2015;29(7):847–851. doi: 10.1097/QAD.0000000000000618. - DOI - PMC - PubMed
    1. Han J, Wang Y, Gan X, Song J, Sun P, Dong XP. Serum cytokine profiles of children with human enterovirus 71-associated hand, foot, and mouth disease. J Med Virol. 2014;86(8):1377–1385. doi: 10.1002/jmv.23929. - DOI - PubMed
    1. Ndumbi P, Gilbert L, Tsoukas CM. Comprehensive Evaluation of the Immune Risk Phenotype in Successfully Treated HIV-Infected Individuals. PLoS One. 2015;10(2):e0117039. doi: 10.1371/journal.pone.0117039. - DOI - PMC - PubMed

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