TY - JOUR
T1 - Interlaboratory reproducibility of female genital tract cytokine measurements by Luminex
T2 - Implications for microbicide safety studies
AU - Scott, Mark E.
AU - Wilson, Sarah S.
AU - Cosentino, Lisa A.
AU - Richardson, Barbra A.
AU - Moscicki, Anna Barbara
AU - Hillier, Sharon L.
AU - Herold, Betsy C.
N1 - Funding Information:
The authors thank Dr. Craig Cohen, protocol chair of the VivaGel Phase I trial, for making specimens available for this study and for facilitating pre-submission review of the manuscript by the STI Clinical Trials Group Executive Committee. This study was supported by the National Institutes of Health (NIH) Grants AI065309 from the National Institute of Allergy and Infectious Diseases (NIAID) and R37 CA051323 from the National Cancer Institute, and by the STI Clinical Trials Group (NIAID Division of Microbiology and Infectious Diseases HHSN266200400074C). In addition, this research was supported by NIH/NCRR UCSF-CTSI Grant Number UL1 RR024131 from the National Center for Research Resources (NCRR). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Information on NCRR is available at http://www.ncrr.nih.gov . Information on Re-engineering the Clinical Research Enterprise can be obtained from http://nihroadmap.nih.gov/clinicalresearch/overview-translational.asp .
PY - 2011/11
Y1 - 2011/11
N2 - The interlaboratory reproducibility of cytokine measurements from cervicovaginal samples by Luminex has not been reported. Using cervicovaginal lavage specimens collected on three study days from 12 women participating in a Phase I microbicide study, we measured a panel of eight cytokines in three independent laboratories. Four (IFN-γ, IL-10, IL-17, and TNF) were below the limit of detection in the majority (85%) of samples in either two or all three laboratories, an observation that may guide analyte selection for future studies. Good interlaboratory agreement (intraclass correlation coefficient, r>0.7) in absolute levels was observed for IL-1β, IL-6, and IL-8, while poor agreement was seen for IFN-α2 (r=0.47). When considering within-subject change from baseline (pre-product, at study-day 0) to either post-product visit (study-days 7 and 14), IL-1β and IL-6 exhibited good interlaboratory agreement (r>0.7), while IFN-α2 and IL-8 did not. Future studies addressing the clinical utility of specific biomarkers of inflammation for microbicide trials should consider reproducibility in the context of defining biologically meaningful thresholds of change for candidate biomarkers, ensuring that such change can be reliably distinguished from background variability.
AB - The interlaboratory reproducibility of cytokine measurements from cervicovaginal samples by Luminex has not been reported. Using cervicovaginal lavage specimens collected on three study days from 12 women participating in a Phase I microbicide study, we measured a panel of eight cytokines in three independent laboratories. Four (IFN-γ, IL-10, IL-17, and TNF) were below the limit of detection in the majority (85%) of samples in either two or all three laboratories, an observation that may guide analyte selection for future studies. Good interlaboratory agreement (intraclass correlation coefficient, r>0.7) in absolute levels was observed for IL-1β, IL-6, and IL-8, while poor agreement was seen for IFN-α2 (r=0.47). When considering within-subject change from baseline (pre-product, at study-day 0) to either post-product visit (study-days 7 and 14), IL-1β and IL-6 exhibited good interlaboratory agreement (r>0.7), while IFN-α2 and IL-8 did not. Future studies addressing the clinical utility of specific biomarkers of inflammation for microbicide trials should consider reproducibility in the context of defining biologically meaningful thresholds of change for candidate biomarkers, ensuring that such change can be reliably distinguished from background variability.
KW - Cervicovaginal secretions
KW - Cytokine measurement
KW - Microbicide studies
KW - Multiplex methods
KW - Reproducibility
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U2 - 10.1016/j.cyto.2011.06.011
DO - 10.1016/j.cyto.2011.06.011
M3 - Article
C2 - 21764598
AN - SCOPUS:80053310620
SN - 1043-4666
VL - 56
SP - 430
EP - 434
JO - Cytokine
JF - Cytokine
IS - 2
ER -