Reproducibility of serum cytokines in an elderly population

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Reproducibility of serum cytokines in an elderly population Jing Guo1, Nicole Schupf1,2,3,4, Richard P. Mayeux1,2,3,4 and Yian Gu1,2,3,4*

Abstract Background: It is important to assess the temporal reproducibility of circulating cytokines for their utility in epidemiological studies. However, existing evidence is limited and inconsistent, especially for the elderly population. Methods: Sixty-five elderly (mean age = 77.89 ± 6.14 years) subjects were randomly selected from an existing prospective cohort study. Levels of 41 cytokines in 195 serum samples, collected at three separate visits that were up to 15.26 years apart, were measured by the Luminex technology. The temporal reproducibility of cytokines was estimated by the intraclass correlation coefficient (ICC) calculated using a mixed-effects model. In addition, data analyses were stratified by the median (4.49 years) of time intervals across sample collection. Sensitivity analyses were performed when excluding subjects with undetectable samples. Results: A total of 23 cytokines were detectable in more than 60% of samples. Fair to good (ICC = 0.40 to 0.75) and excellent (ICC > 0.75) reproducibility was found in 10 (Eotaxin, VEGF, FGF-2, G-CSF, MDC, GM-CSF, TGFα, IP-10, MIP1β, IL-1RA) and 5 (GRO, IFNγ, IL-17, PDGF-AA, IL-4) cytokines, respectively. The results were not changed dramatically in the stratification and sensitivity analyses. Conclusions: Serum levels of the selected 15 cytokines measured with Luminex technology displayed fair to excellent within-person temporal reproducibility among elderly population. Keywords: Reproducibility, Serum, Cytokines, Elderly population

Background Cytokines are secreted polypeptides or glycoproteins that regulate proliferation, apoptosis, and angiogenesis, and involved in the development and progression of various diseases [1]. Cytokine-mediated intercellular communication is regarded as the main mechanism of crosstalk between immune cells [2]. Cytokine and other inflammatory biomarkers play important roles in the pathophysiology of chronic inflammatory diseases [3], cardiovascular diseases [4], neuroinflammation [5], asthma [6], and cancer [7].

* Correspondence: [email protected] 1 Taub Institute for Research in Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY, USA 2 Department of Neurology, Columbia University, New York, NY, USA Full list of author information is available at the end of the article

Circulating inflammatory molecules are widely used in epidemiological studies to investigate their association with chronic diseases [8–10]. In some population-based studies, especially the large-scale cohort studies with a long follow-up period, a single measure of blood sample collected at baseline is usually employed to represent the long-term state of inflammation of participants. However, high intra-individual variability of cytokines may lead to a misclassification of inflammatory status and biased association analyses. Therefore, it is important to establish t