Assessing the Preanalytical Variability of Plasma and Cerebrospinal Fluid Processing and Its Effects on Inflammation-Related Protein Biomarkers.
Assessing the Preanalytical Variability of Plasma and Cerebrospinal Fluid Processing and Its Effects on Inflammation-Related Protein Biomarkers.
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DOI：
10.1016/j.mcpro.2021.100157
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Kockum I
中科院分区：
文献类型：
--
作者：
Huang J;Khademi M;Lindhe Ö;Jönsson G;Piehl F;Olsson T;Kockum I
Proteomics studies are important for the discovery of new biomarkers as clinical tools for diagnosis and disease monitoring. However, preanalytical variations caused by differences in sample handling protocol pose challenges for assessing biomarker reliability and comparability between studies. The purpose of this study was to examine the effects of delayed centrifuging on measured protein levels in plasma and cerebrospinal fluid (CSF). Blood from healthy individuals and patients with multiple sclerosis along with CSF from patients with suspected neurological disorders were left at room temperature for different periods (blood: 1, 24, 48, 72 h; CSF: 1 and 6 h) prior to centrifuging. Ninety-one inflammation-related proteins were analyzed using a proximity extension assay, a high-sensitivity multiplex immunoassay. Additional metabolic and neurology-related markers were also investigated in CSF. In summary, many proteins, particularly in plasma, had increased levels with longer delays in processing likely due in part to intracellular leakage. Levels of caspase 8, interleukin 8, interleukin 18, sirtuin 2, and sulfotransferase 1A1 increased 2-fold to 10-fold in plasma after 24 h at room temperature. Similarly, levels of cathepsin H, ectonucleoside triphosphate diphosphohydrolase 5, and WW domain containing E3 ubiquitin protein ligase 2 differentiated in CSF with <6 h delay in processing. However, the rate of change for many proteins was relatively consistent; therefore, we were able to characterize biomarkers for detecting sample handling variability. Our findings highlight the importance of timely and consistent sample collection and the need for increased awareness of protein susceptibility to sample handling bias. In addition, suggested biomarkers may be used in certain situations to detect and correct for preanalytical variation in future studies. Several blood and cerebrospinal fluid proteins are affected by sample handling. Plasma protein levels increased with longer centrifugation delay from hemolysis. Certain proteins may assess sample handling variability and predict delay time. We assessed the effects of delayed sample handling on a panel of 92 inflammation-related proteins in the blood and cerebrospinal fluid. Plasma protein levels were measured at delayed centrifugation times of 1, 24, 48, and 72 h corresponding with common postal-transit delays, and changes in relative concentration were modeled and validated using an external dataset. Several proteins were selected as markers of assessing sample handling variability for application in future studies.
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影响因子：
20.3
作者：
Khan, Samina Yasmin;Kelher, Marguerite R.;Silliman, Christopher C.
通讯作者：
Silliman, Christopher C.
影响因子：
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作者：
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通讯作者：
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影响因子：
6
作者：
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通讯作者：
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影响因子：
5.8
作者：
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通讯作者：
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影响因子：
3.2
作者：
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通讯作者：
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