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.
Cancer Epidemiol Biomarkers Prev. 2013 Nov;22(11):2009-15. doi: 10.1158/1055-9965.EPI-13-0379. Epub 2013 Aug 27.
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.
前瞻性队列研究通常在单个时间点量化血清免疫生物标志物，以确定癌症和其他多年后发生的慢性疾病的风险。个体内血清标志物时间稳定性的估计部分评估了单个生物标志物测量的效用，并且可能对慢性疾病风险的前瞻性研究设计具有重要意义。
使用在大约 2 年内的 3 次就诊期间从 200 名 HIV 血清阴性男性中收集的存档血清，在一个实验室中测量了 14 种生物标志物（ApoA1、sCD14、sgp130、sIL-6R、sIL-2Rα、sTNFR2、BAFF/BLyS、CXCL13、IFN-γ、白细胞介素[IL]-1β、IL-6、IL-8、IL-10 和 TNF-α）的浓度。为每个生物标志物计算了年龄和种族调整后的组内相关系数（ICC），并使用混合线性回归模型来检查年龄、种族、季节和研究地点对生物标志物浓度的影响。
在所有 3 次研究就诊中，大多数生物标志物的 ICC 值表明个体内稳定性良好到优秀。ApoA1（ICC=0.88）和 TNF-α（ICC=0.87）表现出最大的稳定性；IL-8 的 ICC（ICC=0.33）明显不太稳定。当计算连续两次就诊之间的 ICC 时，ICC 值相似。协变量不会影响生物标志物水平或其时间稳定性。所有生物标志物在就诊时均显示出中等至强的两两相关性。
在 2 年期间，评估的大多数免疫生物标志物的血清浓度表现出可接受的个体内时间可靠性。可能需要进一步调查以澄清 IL-8 的稳定性。
这些发现支持在研究与慢性疾病关联的前瞻性研究中使用这些血清免疫生物标志物。
