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Cancer Epidemiol Biomarkers Prev. 2013 Nov;22(11):2009-15. doi: 10.1158/1055-9965.EPI-13-0379. Epub 2013 Aug 27.

Temporal stability of serum concentrations of cytokines and soluble receptors measured across two years in low-risk HIV-seronegative men.

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Authors' Affiliations: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; UCLA AIDS Institute, and Departments of Psychiatry & Biobehavioral Sciences and Obstetrics & Gynecology, David Geffen School of Medicine at UCLA; Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California; Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Medicine-Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Departments of Molecular Microbiology and Immunology and Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Microbiology, Immunology & Molecular Genetics, and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, California.



Prospective cohort studies often quantify serum immune biomarkers at a single time point to determine risk of cancer and other chronic diseases that develop years later. Estimates of the within-person temporal stability of serum markers partly assess the utility of single biomarker measurements and may have important implications for the design of prospective studies of chronic disease risk.


Using archived sera collected from 200 HIV-seronegative men at three visits spaced over approximately 2 years, concentrations of 14 biomarkers (ApoA1, sCD14, sgp130, sIL-6R, sIL-2Rα, sTNFR2, BAFF/BLyS, CXCL13, IFN-γ, interleukin [IL]-1β, IL-6, IL-8, IL-10, and TNF-α) were measured in a single laboratory. Age- and ethnicity-adjusted intraclass correlation coefficients (ICC) were calculated for each biomarker, and mixed linear regression models were used to examine the influence of age, ethnicity, season, and study site on biomarker concentrations.


Across all three study visits, most biomarkers had ICC values indicating fair to excellent within-person stability. ApoA1 (ICC = 0.88) and TNF-α (ICC = 0.87) showed the greatest stability; the ICC for IL-8 (ICC = 0.33) was remarkably less stable. The ICCs were similar when calculated between pairs of consecutive visits. The covariables did not influence biomarker levels or their temporal stability. All biomarkers showed moderate to strong pairwise correlations across visits.


Serum concentrations of most evaluated immune biomarkers displayed acceptable to excellent within-person temporal reliability over a 2-year period. Further investigation may be required to clarify the stability of IL-8.


These findings lend support to using these serologic immune biomarkers in prospective studies investigating associations with chronic diseases.

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