Reliability, stability during long-term storage, and intra-individual variation of circulating levels of osteopontin, osteoprotegerin, vascular endothelial growth factor-A, and interleukin-17A
Abstract Background Studies in many populations have reported associations between circulating cytokine levels and various physiological or pathological conditions. However, the reliability of cytokine measurements in population studies, which measure cytokines in multiple assays over a prolonged pe...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | European Journal of Medical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40001-024-01722-w |
| _version_ | 1797275361288912896 |
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| author | Tomoki Nakamizo John Cologne Takeshi Kishi Tetsuya Takahashi Mayumi Inoue Hiroyuki Ryukaku Tomonori Hayashi Yoichiro Kusunoki Saeko Fujiwara Waka Ohishi |
| author_facet | Tomoki Nakamizo John Cologne Takeshi Kishi Tetsuya Takahashi Mayumi Inoue Hiroyuki Ryukaku Tomonori Hayashi Yoichiro Kusunoki Saeko Fujiwara Waka Ohishi |
| author_sort | Tomoki Nakamizo |
| collection | DOAJ |
| description | Abstract Background Studies in many populations have reported associations between circulating cytokine levels and various physiological or pathological conditions. However, the reliability of cytokine measurements in population studies, which measure cytokines in multiple assays over a prolonged period, has not been adequately examined; nor has stability during sample storage or intra-individual variation been assessed. Methods We assessed (1) analytical reliability in short- and long-term repeated measurements; (2) stability and analytical reliability during long-term sample storage, and (3) variability within individuals over seasons, of four cytokines—osteopontin (OPN), osteoprotegerin (OPG), vascular endothelial growth factor-A (VEGF-A), and interleukin-17A (IL-17A). Measurements in plasma or serum samples were made with commercial kits according to standard procedures. Estimation was performed by fitting a random or mixed effects linear model on the log scale. Results In repeated assays over a short period, OPN, OPG, and VEGF-A had acceptable reliability, with intra- and inter-assay coefficients of variation (CV) less than 0.11. Reliability of IL-17A was poor, with inter- and intra-assay CV 0.85 and 0.43, respectively. During long-term storage, OPG significantly decayed (− 33% per year; 95% confidence interval [− 54, − 3.7]), but not OPN or VEGF-A (− 0.3% or − 6.3% per year, respectively). Intra- and inter-assay CV over a long period were comparable to that in a short period except for a slight increase in inter-assay CV of VEGF-A. Within-individual variation was small for OPN and VEGF-A, with intra-class correlations (ICC) 0.68 and 0.83, respectively, but large for OPG (ICC 0.11). Conclusions We conclude that OPN and VEGF-A can be reliably measured in a large population, that IL-17A is suitable only for small experiments, and that OPG should be assessed with caution due to degradation during storage and intra-individual variation. The overall results of our study illustrate the need for validation under relevant conditions when measuring circulating cytokines in population studies. |
| first_indexed | 2024-03-07T15:13:15Z |
| format | Article |
| id | doaj.art-9ce9561e37254aa4926bcd64cb63c33a |
| institution | Directory Open Access Journal |
| issn | 2047-783X |
| language | English |
| last_indexed | 2024-03-07T15:13:15Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj.art-9ce9561e37254aa4926bcd64cb63c33a2024-03-05T18:04:38ZengBMCEuropean Journal of Medical Research2047-783X2024-02-012911810.1186/s40001-024-01722-wReliability, stability during long-term storage, and intra-individual variation of circulating levels of osteopontin, osteoprotegerin, vascular endothelial growth factor-A, and interleukin-17ATomoki Nakamizo0John Cologne1Takeshi Kishi2Tetsuya Takahashi3Mayumi Inoue4Hiroyuki Ryukaku5Tomonori Hayashi6Yoichiro Kusunoki7Saeko Fujiwara8Waka Ohishi9Department of Clinical Studies, RERFDepartment of Statistics, RERFDivision of Clinical Laboratories, RERFFaculty of Rehabilitation, Hiroshima International UniversityDivision of Clinical Laboratories, RERFDivision of Clinical Laboratories, RERFDepartment of Molecular Biosciences, RERFDepartment of Molecular Biosciences, RERFFaculty of Pharmacy, Yasuda Women’s UniversityDepartment of Clinical Studies, RERFAbstract Background Studies in many populations have reported associations between circulating cytokine levels and various physiological or pathological conditions. However, the reliability of cytokine measurements in population studies, which measure cytokines in multiple assays over a prolonged period, has not been adequately examined; nor has stability during sample storage or intra-individual variation been assessed. Methods We assessed (1) analytical reliability in short- and long-term repeated measurements; (2) stability and analytical reliability during long-term sample storage, and (3) variability within individuals over seasons, of four cytokines—osteopontin (OPN), osteoprotegerin (OPG), vascular endothelial growth factor-A (VEGF-A), and interleukin-17A (IL-17A). Measurements in plasma or serum samples were made with commercial kits according to standard procedures. Estimation was performed by fitting a random or mixed effects linear model on the log scale. Results In repeated assays over a short period, OPN, OPG, and VEGF-A had acceptable reliability, with intra- and inter-assay coefficients of variation (CV) less than 0.11. Reliability of IL-17A was poor, with inter- and intra-assay CV 0.85 and 0.43, respectively. During long-term storage, OPG significantly decayed (− 33% per year; 95% confidence interval [− 54, − 3.7]), but not OPN or VEGF-A (− 0.3% or − 6.3% per year, respectively). Intra- and inter-assay CV over a long period were comparable to that in a short period except for a slight increase in inter-assay CV of VEGF-A. Within-individual variation was small for OPN and VEGF-A, with intra-class correlations (ICC) 0.68 and 0.83, respectively, but large for OPG (ICC 0.11). Conclusions We conclude that OPN and VEGF-A can be reliably measured in a large population, that IL-17A is suitable only for small experiments, and that OPG should be assessed with caution due to degradation during storage and intra-individual variation. The overall results of our study illustrate the need for validation under relevant conditions when measuring circulating cytokines in population studies.https://doi.org/10.1186/s40001-024-01722-wMolecular epidemiologyBiomarkersCytokinesBiological variationIndividualReproducibility of results |
| spellingShingle | Tomoki Nakamizo John Cologne Takeshi Kishi Tetsuya Takahashi Mayumi Inoue Hiroyuki Ryukaku Tomonori Hayashi Yoichiro Kusunoki Saeko Fujiwara Waka Ohishi Reliability, stability during long-term storage, and intra-individual variation of circulating levels of osteopontin, osteoprotegerin, vascular endothelial growth factor-A, and interleukin-17A European Journal of Medical Research Molecular epidemiology Biomarkers Cytokines Biological variation Individual Reproducibility of results |
| title | Reliability, stability during long-term storage, and intra-individual variation of circulating levels of osteopontin, osteoprotegerin, vascular endothelial growth factor-A, and interleukin-17A |
| title_full | Reliability, stability during long-term storage, and intra-individual variation of circulating levels of osteopontin, osteoprotegerin, vascular endothelial growth factor-A, and interleukin-17A |
| title_fullStr | Reliability, stability during long-term storage, and intra-individual variation of circulating levels of osteopontin, osteoprotegerin, vascular endothelial growth factor-A, and interleukin-17A |
| title_full_unstemmed | Reliability, stability during long-term storage, and intra-individual variation of circulating levels of osteopontin, osteoprotegerin, vascular endothelial growth factor-A, and interleukin-17A |
| title_short | Reliability, stability during long-term storage, and intra-individual variation of circulating levels of osteopontin, osteoprotegerin, vascular endothelial growth factor-A, and interleukin-17A |
| title_sort | reliability stability during long term storage and intra individual variation of circulating levels of osteopontin osteoprotegerin vascular endothelial growth factor a and interleukin 17a |
| topic | Molecular epidemiology Biomarkers Cytokines Biological variation Individual Reproducibility of results |
| url | https://doi.org/10.1186/s40001-024-01722-w |
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