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Intraindividual variability over time in plasma biomarkers of inflammation and effects of long-term storage

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Abstract

Purpose

Systemic measures of chronic inflammation, often based on a single blood draw, are frequently used to study the associations between inflammation and chronic diseases such as cancer. However, more information is needed on the measurement error in these markers due to laboratory error, within-person variation over time, and long-term storage.

Methods

We investigated the intraindividual variability of inflammation markers C-reactive protein (CRP), interleukin-6 (IL-6), and soluble tumor necrosis factor receptors I and II (sTNFRI and II) in a subsample of the Seattle Barrett’s esophagus study cohort. Two fasting blood samples were collected between 1995 and 2009 from 360 participants on average 1.8 years apart. CRP, IL-6, and sTNF receptor levels were measured by immunonephelometry, ELISA, and multiplex assays, respectively. Intra- and inter-batch coefficients of variation (CV) were estimated using blinded pooled samples within each batch. Intraclass correlations (ICCs) were computed using random effects ANOVA.

Results

Intra- and inter-batch CVs for the pooled plasma aliquots were low (2.4–8.9 %), suggesting little laboratory variability. Reliability over time was excellent for sTNF receptors (ICCsTNF-RI = 0.89, ICCsTNF-RII = 0.85) and fair-to-good for CRP and IL-6 (ICCCRP = 0.55, ICCIL-6 = 0.57). For samples stored for over 13 years, the ICCs for CRP and IL-6 were decreased but those for sTNF receptors were unaffected.

Conclusion

sTNF receptor levels are more stable within person over time than CRP or IL-6. Long-term storage of samples appears to increase the variability of CRP and IL-6 measures, while the reliability of soluble TNF receptor measures was not affected by storage time.

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Acknowledgments

We thank Tricia Christopherson for project management; Terri Watson for database management; and Christine Karlsen for coordination of patient care.

Financial support

This work was supported by United States National Institutes of Health (Grants P01CA091955, K05CA124911 and R25CA094880). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Sheetal Hardikar, Xiaoling Song, Mario Kratz, Garnet L. Anderson, Patricia L. Blount, Brian J. Reid, Thomas L. Vaughan & Emily White

  2. Department of Epidemiology, University of Washington, Seattle, WA, USA

    Sheetal Hardikar, Mario Kratz, Thomas L. Vaughan & Emily White

  3. Department of Genome Sciences, University of Washington, Seattle, WA, USA

    Mario Kratz & Brian J. Reid

  4. Department of Biostatistics, University of Washington, Seattle, WA, USA

    Garnet L. Anderson

  5. Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Patricia L. Blount & Brian J. Reid

  6. Department of Medicine, University of Washington, Seattle, WA, USA

    Patricia L. Blount & Brian J. Reid

  7. 1100 Fairview Ave. N., M4-B402, PO Box 19024, Seattle, WA, 98109-1024, USA

    Sheetal Hardikar

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  1. Sheetal Hardikar
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Correspondence to Sheetal Hardikar.

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Hardikar, S., Song, X., Kratz, M. et al. Intraindividual variability over time in plasma biomarkers of inflammation and effects of long-term storage. Cancer Causes Control 25, 969–976 (2014). https://doi.org/10.1007/s10552-014-0396-0

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  • DOI: https://doi.org/10.1007/s10552-014-0396-0

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