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Lab-on-a-Chip Immunoassay Systems
Published in Richard O’Kennedy, Caroline Murphy, Immunoassays, 2017
Barry Byrne, Louise M. Barrett
Disease biomarkers are analytes (typically proteinaceous), which are detected at elevated levels in a biological sample, such as blood, urine or saliva, during the onset and progression of disease. Their presence is indicative of the disease trait (e.g. risk factor), the disease state (e.g. pre-clinical or clinical) and the disease rate (progression) [81]. Cardiovascular disease (CVD) is a major killer which places a considerable financial burden on healthcare systems and accounts for approximately half of all deaths in the western world. Biomarkers of inflammation, ventricular overload, myocardial necrosis and myocardial ischemia can readily be detected in blood [82], and a selection of the ‘lab-on-a-chip’ immunodiagnostic platforms that have been developed to facilitate their detection is highlighted in Table 5.3. While this table is not exhaustive, in that it does not highlight every single microfluidic immunoassay developed to date for detecting CVD-related disease markers, it does focus on the detection of five targets of great clinical relevance. C-reactive protein (CRP) is a 125 kDa acute-phase reactant produced in the liver, and a well-established marker of inflammation. This highly stable protein is a member of the pentraxin family, and is comprised of five symmetric units (approximately 206 amino acids) which are covalently bound to one another [83]. Interestingly, Khreiss et al. [84] investigated the mechanism by which CRP activates endothelial cells and demonstrated that the loss of pentameric symmetry was conducive to the induction of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), which both play key roles in leucocyte recruitment. Furthermore, the observation that serum CRP concentrations increase by a factor of 10,000 during the acute-phase response [85] suggests that this biomarker is of great clinical significance. The lab-on-a-chip immunoassays summarised in Table 5.3 for CRP detection [86, 87] demonstrate how the integration of elegant microfluidic design and a sensitive antibody can be used to detect this biomarker, with blood selected as an analytical sample in the latter example.
The effect of exposure to crude oil on the immune system. Health implications for people living near oil exploration activities
Published in International Journal of Environmental Health Research, 2021
Pauline McLoone, Olzhas Dyussupov, Zhaxybek Nurtlessov, Ussen Kenessariyev, Dinara Kenessary
Bohne-Kjersem et al. (2009) assessed the effects of crude North Sea oil on plasma protein changes in juvenile Atlantic cod (Gadus morhua) using proteomics (including 2-D electrophoresis image analysis and mass spectrometry). The fish were exposed to low, medium or high levels of crude oil in their tanks (at 0.06, 0.25, or 1.0 mg/L) for up to 24 days and samples were taken on Days 3, 14, and 24. Proteins involved in the immune system that were altered by the crude oil exposure included up-regulated levels of α-1 antitrypsin (A1AT) and pentraxin, and down-regulated levels of serotransferrin, α-enolase, and hemopexin. A1AT is an anti-inflammatory liver-derived acute-phase protein that plays an important role in protecting the host from inflammation (Bergin et al. 2012; Ehlers 2014). Pentraxins are fluid-phase pattern recognition molecules that play a key role in innate immune defense and inflammation; members of the pentraxin family include the acute phase protein, C-reactive protein (Bottazzi et al. 2016). α-enolase is involved in autoimmune diseases, i.e., as an autoantigen in rheumatoid arthritis, and to impart both pro- and anti-inflammatory activities (Guillou et al. 2016). Serotransferrin and hemopexin play roles in regulation of cellular iron levels; down-regulation of these two molecules could result in increased cellular iron levels in immune cells (Anderson and Frazer 2005). Because of the increased iron burdens, macrophages (for example) might undergo alterations in cellular functions, such as increased nitric oxide (NO) and reactive oxygen species production (Crichton et al. 2002). Hemopexin also modulates levels of T-helper cell phenotypes in autoimmune diseases (Rolla et al. 2013).