Novel biomarkers for acute phase reactants
Article information
Acute phase reactants (APRs) are defined by plasma concentrations that increase (positive APR) or decrease (negative APR) by at least 25% during inflammatory disorders [1]. C-reactive protein (CRP) is an APR synthesized by the liver in response to interleukin 6 (IL-6) and the most frequently studied conventional biomarker of inflammation [2]. Recently, novel biomarkers for acute inflammation such as serum amyloid A (SAA), procalcitonin, presepsin, and calprotectin have been introduced in clinical laboratories. In this brief review, we outline the characteristics and advantages of these biomarkers.
SERUM AMYLOID A
SAA was discovered a quarter of a century ago as a plasma component that shares antigenicity with amyloid AA, a fibrillogenic precursor in amyloidosis [3]. This component can increase by 100- to 1,000-fold over the baseline level of approximately 1 μg/mL during acute phase reactions [3]. CRP has become the gold standard in the management of inflammatory diseases, but SAA has major advantages over CRP tests. First, the amplitude of the increase of SAA is greater than that of CRP [4], especially in viral infections such as measles, adenovirus, mumps, rubella, varicella and influenza, in which SAA levels are often elevated even when CRP is below the detection level [5]. Second, SAA more accurately predicts poor prognosis of elderly inpatients than does CRP [4]. SAA can also detect some events such as minor infection which may occur in the elderly and patients with chronic disorders such as diabetes [6]. Third, discrepancies between SAA and CRP have been observed in patients with kidney transplantations [4]. During transplant rejection, SAA is markedly elevated along with serum creatinine and the changes are dramatic enough to be recognized easily [7]. In contrast, CRP response is poor during rejections, not only in the early phases but throughout subsequent days [7]. Therefore, SAA tests can be recommended in clinical conditions in which CRP does not show a useful response. Finally, SAA is a sensitive biomarker with potential to assess disease severity and survival outcomes in COVID-19 patients and a better choice than CRP for predicting the prognosis of patients with COVID-19 [8].
PROCALCITONIN AND PRESEPSIN
Sepsis is a life-threatening condition characterized by organ failure and is a result of a dysregulated host response to infection [9]. Serum procalcitonin (PCT) levels increase to very high values in patients with severe invasive bacterial infections compared to patients with mild local bacterial infections or viral infections [10]. PCT is a biomarker that can be used to differentiate sepsis from noninfectious triggers of systemic inflammatory response syndrome in critically ill patients [10]. However, PCT can be increased in some disorders, especially following trauma without the presence of infection [9,11]. Compared with other markers, presepsin may have better sensitivity and specificity for the diagnosis of sepsis [12]. The sensitivity of presepsin for the diagnosis of sepsis was 91.9%, PCT 89.9%, IL-6 88.9%, and blood culture 35.4%, suggesting that presepsin has good performance for the diagnosis of sepsis, and that PCT has nearly equal performance compared to presepsin for detecting sepsis [12,13]. However, presepsin increases earlier and faster in patients with sepsis 2 hours after infection, peaks at 3 hours, and declines at 4 to 8 hours [12]. Compared with presepsin, PCT increases within 4 hours after infection, reaches a plateau at 8 to 24 hours, and peaks 24 hours after infection [12]. In the emergency department, presepsin is most useful because it increases in plasma earlier than other biomarkers [9].
CALPROTECTIN
Calprotectin (CLP) is a stable heteromorphic dimer of S100A8 and S100A9 [14]. CLP plays an important role in the inflammatory cascade and has a wide range of proinflammatory functions such as cytokine promotion, chemokine production, and leukocyte aggregation, adhesion, and migration [15]. According to a previous report, serum CLP levels increase in close correlation with traditional markers of oxidative stress and inflammation [16]. Increased plasma calprotectin levels have been found in inflammatory chronic diseases such as inflammatory bowel diseases, rheumatoid arthritis, systemic lupus erythematosus, juvenile idiopathic arthritis, multiple sclerosis, and cystic fibrosis [17]. Moreover, it was independently associated with mortality, functional dependence, and hemorrhagic transformation in acute ischemic stroke [18]. In patients with aneurysmal subarachnoid hemorrhage, serum CLP levels show significant correlations with severity and the poor prognosis [18]. Serum CLP has also recently been suggested as a novel biomarker for acute brain injury, as its levels are closely related to inflammatory reaction after severe traumatic brain injury [18].
CONCLUSION
Emerging studies present a broad spectrum of novel biomarkers in inflammation and infection. Novel biomarkers, such as various APRs, can greatly aid in the differential diagnosis and prognosis of inflammatory and infectious disease. In addition, clinicians will benefit from earlier availability of blood test results, with many new inflammatory biomarkers showing rapid diagnosis of disease and prompt reflection of changes in patient status.
Notes
Conflicts of interest
The author has no conflicts of interest to declare.
Funding
The author received no financial support for this study.
Data availability
Data sharing is not applicable as no new data were created or analyzed in this study.