At present, the commonly used infection markers in clinical practice mainly include C-reactive protein (CRP), procalcitonin (PCT), serum amyloid A (Serum amyloid A, SAA) and interleukin 6 (Interleukin 6, IL-6). However, what are the similarities and differences between the four as the same infection markers? What are their unique characteristics? What role does it play in clinical differential diagnosis?
Today, we take a look at the characteristics and clinical significance of the four, hoping to help you better understand.
1. C-reactive protein
CRP is one of the acute phase-reactive proteins and one of the most commonly used indicators of infection, which is produced by cytokine-mediated synthesis by the liver, binds to ligands (phosphorylcholine of cells or bacteria, etc.), activates complement and mononuclear phagocyte systems, and clears pathogens or pathological cells with ligands to maintain homeostasis.
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Typically, CRP begins to rise 6 to 8 hours after infection and peaks at 24 to 48 hours, hundreds of times higher than normal, while the magnitude of CRP elevation is positively correlated with the degree of infection.
Because of this correlation, clinicians often monitor the dynamics of CRP when treating bacterial infections with antibiotics, and CRP can be alerted to complications and the effectiveness of treatment earlier than other clinical signs.
However, CRP is usually not elevated during viral infection (except for some viruses that cause tissue damage such as adenovirus, herpes virus, etc.), so CRP can also be used as a differential diagnostic indicator of bacterial infection and viral infection.
Hypersensitive C-reactive protein (hs-CRP) is a supersensitive detection technology that can accurately detect low concentrations of C-reactive protein, which is a sensitive index for identifying low-level inflammatory states, greatly improving the sensitivity of analysis.
Second, procalcitonin
PCT is a calcitonin propeptide substance without hormone activity, which has no hormonal activity itself, while calcitonin has the effect of reducing blood calcium concentration. Under normal circumstances, PCT is produced only by the neuroendocrine cells of thyroid C cells and lungs, but almost all parenchymal tissue cells can synthesize PCT when the body is infected by microorganisms.
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Therefore, in the state of inflammatory stimulation, especially severe bacterial infection or sepsis, pcT can be generated in various tissues and multiple cell types of the body and released into the circulatory system, at this time, its level in plasma is significantly increased.
The Expert Consensus on the Clinical Application of Procalcitonin Pro-PCT in Emergency Medicine, published in September 2012, also states that PCT levels in patients with sepsis are significantly higher than in patients with non-sepsis, and that elevated PCT is highly specific for sepsis due to bacterial infections, and can be used as a biomarker for diagnosing sepsis and differentiating severe bacterial infections.
Similar to CRP, PCT does not increase or is only mildly elevated in viral diseases, so PCT can also be used as a differential diagnostic indicator of bacterial and viral infections. In addition, pct is more sensitive and specific than traditional markers such as CRP and erythrocyte sedimentation rate when used to differentiate viral diseases.
3. Serum amyloid A
SAA is a precursor to tissue amyloid A and a sensitive acute phase reactive protein synthesized in the liver by activated macrophages and fibroblasts.
Unlike the previous two, SAA is not only elevated when the body is infected with bacteria, but also significantly elevated during viral infection, although it rises more often than in viral infection. In addition, SAA is also a sensitive indicator of early infection, which is more sensitive than CRP, and usually, a negative SAA excludes infection.
In addition, SAA also has the characteristics of fast rise and rapid decline, after the body is infected, it can quickly rise by about 1000 times within 4 to 6 hours; after the pathogen is cleared, it can be rapidly reduced to normal levels, so it can be used as a sensitive indicator reflecting the body's infection and inflammation treatment effect.
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In 2019, the "Expert Consensus on the Clinical Application of Serum Amyloid A in Infectious Diseases", published in the 3rd issue of the Chinese Journal of Laboratory Medicine, stated:
1. Detection of SAA is of great value for assisting in the diagnosis of viral infection, and the SAA level is consistently higher than 10 mg/L and less than 100 mg/L, and the possibility of viral infection is high;
2. The level of SAA in the acute stage of bacterial infection is significantly higher than that in the acute stage of viral infection, and the continuous level of SAA above 100 mg/L has a strong indicative effect on the acute stage of bacterial infection. At the same time, SAA has a high negative predictive value for the diagnosis of neonatal sepsis;
3. SAA can be used as an independent factor to judge the severity of infectious diseases and inflammation such as bacteria and viruses, and greater than 500 mg/L indicates that the condition is serious;
4. In the early diagnosis of infectious diseases, SAA combined with CRP detection can identify viral and bacterial infections early: when SAA and CRP are elevated at the same time, it indicates the possibility of bacterial infection; if SAA is elevated and CRP is not elevated, it indicates the possibility of viral infection.
IV. Interleukin 6
IL-6 is a cytokine of interleukins that is secreted and produced by fibroblasts, monocytes/macrophages, T lymphocytes, B lymphocytes, epithelial cells, keratinocytes, and a variety of tumor cells.
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IL-6 is an important member of the cytokine network and is central in the acute inflammatory response, mediating the liver's acute phase response, inducing crP and PCT, and therefore also predates the appearance of CRP and PCT. Typically, IL-6 rises rapidly after bacterial infection, PCT increases after 2 hours, and CRP increases rapidly after 6 hours, which is also the advantage of IL-6 detection.
Because the rise in IL-6 in the inflammatory response precedes other markers and lasts long, it can be used to aid in the early detection and early diagnosis of acute infection. In addition, the IL-6 half-life is shorter than CRP and PCT, which can respond more quickly to the effects of anti-infective therapy, so dynamic observation of IL-6 levels can also help to understand the progression of infectious disease and response to treatment.
In summary, each of the four has its own advantages
CRP (or hs-CRP) is a common item used to detect inflammation in outpatient and emergency departments, and it is generally not elevated in viral infection, but it should be noted that hs-CRP can be elevated during herpesvirus infection. In addition, hypersensitive C-reactive protein is a protein product under nonspecific stress and may also rise in trauma, stress, immune diseases, or tumors.
PCT appears earlier than CRP and SAA, can be detected in 2 hours, rise significantly in 6 hours, and remain at a high level for 8 to 24 hours. It is highly specific for the diagnosis of sepsis, etc.
SAA is a very sensitive indicator of inflammation, negative can exclude inflammatory infection, has the characteristics of rapid rise and fall, and is significantly elevated in viral infection.
As a traditional indicator of inflammation, IL-6 appears early and has high sensitivity.
The four major inflammatory indicators have their own strengths, in the actual clinical application, it is necessary to combine the specific conditions of patients, choose the corresponding joint test, in order to complement each other's advantages, make full use of their strengths and avoid weaknesses, and can more quickly diagnose and monitor the follow-up treatment of infected patients!
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bibliography:
1.Azoulay E, Echeverria P, Kett D. Candida prophylaxis and therapy in the ICU. Seminars in Respiratory and Critical Care Medicine 2011;32:159e73.
2. Expert consensus group on the clinical application of calcitonin pro-emergency department. Expert consensus on the clinical application of procalcitonin (PCT) in emergency[J]. Chinese Journal of Emergency Medicine,2012,21(9):944-951.
3. Laboratory Medicine Professional Committee of Chinese Association of Integrative Medicine. Expert consensus on the clinical application of serum amyloid A in infectious diseases[J]. Chinese Journal of Laboratory Medicine,2019,42(3):186-192.