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Multiplex assay reliability and long-term intra-individual variation of serologic inflammatory biomarkers.
Abstract
BACKGROUND: Circulating cytokines, chemokines, and soluble cytokine receptors can
serve as biomarkers of inflammation and immune dysregulation. Good reliability of
multiplex platforms, which allow for simultaneous, comprehensive biomarker assessment,
is critical for their utility in epidemiologic studies. We examined the reliability
of the Meso-Scale Discovery (MSD) platform to simultaneously quantitate 15 cytokines
and chemokines and the Luminex platform (R&D Systems) to quantitate 5 soluble receptors
and 2 chemokines and cytokines and evaluated long-term within-person correlation of
these biomarkers. METHODS: The detectability and reliability of these assay systems
were assessed using the same external controls across plates and archived sera from
250 HIV(-) men in the Multicenter AIDS Cohort Study. Using up to four visits per person
from 1984 to 2009, age-adjusted intraclass correlation coefficients (ICC) of biomarkers
with >80% detectability (CCL11, CXCL8, CXCL10, CCL2, CCL4, CCL13, CCL17, CXCL13, IL-10,
IL-12p70, IL-6, TNF-α, BAFF, sCD14, sCD27, sgp130, sIL-2Rα, and sTNF-R2) were obtained
using linear mixed models. RESULTS: Most biomarkers were detectable in 80% of control
samples; IFN-γ, GM-CSF, and IL-2 were undetectable in >20% of samples. Among the HIV-uninfected
men, most biomarkers showed fair to strong within-person correlation (ICC>0.40) up
to 15years. The ICC for CXCL8 was good in the short term but decreased with increasing
time between visits, becoming lower (ICC<0.40) after 8years. CONCLUSIONS: These multiplexed
assays showed acceptable reliability for use in epidemiologic research, despite some
technical variability and limitations in cytokine quantitation. Most biomarkers displayed
moderate-to-excellent intra-individual variability over the long term, suggesting
their utility in prospective studies investigating etiologic associations with diverse
chronic conditions.
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https://hdl.handle.net/10161/13345Published Version (Please cite this version)
10.1016/j.cyto.2016.09.018Publication Info
McKay, Heather S; Margolick, Joseph B; Martínez-Maza, Otoniel; Lopez, Joseph; Phair,
John; Rappocciolo, Giovanna; ... Bream, Jay H (2017). Multiplex assay reliability and long-term intra-individual variation of serologic
inflammatory biomarkers. Cytokine, 90. pp. 185-192. 10.1016/j.cyto.2016.09.018. Retrieved from https://hdl.handle.net/10161/13345.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Thomas Norton Denny
Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine
Institute (DHVI), Associate Dean for Duke Research and Discovery @RTP, and a Professor
of Medicine in the Department of Medicine at Duke University Medical Center. He is
also an Affiliate Member of the Duke Global Health Institute. Previously, he served
on the Health Sector Advisory Council of the Duke University Fuquay School of Business.
Prior to joining Duke, he was an Associate Professor of Pathology, Labo

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