PART01:What is SAA?
★SAA is an acute phase protein produced by liver cells and secreted into the serum. It is mainly degraded by proteins existing in the blood, cell surface and intracellular. The liver is the main site of degradation. In the acute phase, large amounts of cytokines IL-1, IL-6 and TNF-α stimulate liver cells to synthesize and release SAA (see the relationship between IL-6 and SAA).
★The human SAA family has four members: SAA1, SAA2, SAA3 and SAA4. According to the expression in the body, the SAA1 and SAA2 genes synthesize SAA1 and SAA2 proteins, which are called acute phase SAA (A-SAA). They are more abundant in the acute phase. It can be synthesized in all kinds of cells. The SAA3 gene has a coding shift of 1 base insertion in one of its exons, causing a translation termination signal there, and is a pseudogene; the SAA4 gene synthesizes constitutive SAA (C-SAA). , expressed at low levels in the liver, and C-SAA concentration does not change with pathological (illness) changes. In conventional SAA testing, they all refer to A-SAA.
★The content of SAA in the normal human body is low. After the body is stimulated (inflammation, infection, injury, tumor, etc.), it produces a series of cytokines to regulate the increase in the expression of A-SAA, becoming the main SAA in the body at this time. Studies have found that a variety of cells, including normal tissue cells, tumor cells, and atherosclerotic plaques, can synthesize A-SAA, suggesting that SAA synthesized in extrahepatic tissue cells can serve as an immune defense molecule to resist local inflammatory damage.
★SAA concentration begins to increase 3 to 6 hours after infection, with a half-life of about 50 minutes, and the increase can reach 10 to 1,000 times the normal value. After the pathogen is eliminated, it can quickly reduce to normal levels, which is a sensitive indicator reflecting the body's infection status and inflammation recovery.
★SAA is mainly degraded by proteases present in the blood, on cell surfaces and within cells, and the liver is its main site of degradation. Since SAA is insoluble in water, the SAA produced by the body quickly combines with HDL after entering the blood, changing the characteristics of HDL particles, making them larger and denser, affecting the body's cholesterol metabolism. SAA can be degraded only after it is dissociated from HDL, and HDL can inhibit the degradation of SAA. When the body is in an inflammatory state, SAA synthesis increases and degradation slows down, causing SAA in the blood to continue to increase. SAA produced by extrahepatic cells is mainly degraded by proteases on the cell surface or within the cells through intercellular adhesion and endocytosis.
★The value of SAA (A-SAA) can be traced to the WHO international standard NIBSC code: 92/680.
★For SAA detected on a blood routine instrument, the whole blood sample has good consistency with the serum/plasma sample after being calibrated by HCT (automatic calibration of the instrument).
★Quantitative methods are recommended for the detection of SAA, and NMPA-approved methods such as immunoscattering turbidimetry can be used. When the SAA in the blood is <10 mg/L, it indicates that the risk of infection is not high; when the SAA in the blood is ≥10 mg/L, the risk of infection is increased.
★Some studies have shown that SAA may not be transported across the placenta, and elevated cord blood SAA may be evidence of neonatal infection.
★SAA is not affected by age and gender.
PART02: What is the clinical significance of SAA?
★Application in viral infections: SAA is an acute phase response protein, which is significantly increased in the acute phase of various viral infections. This is one of the reasons why it is recommended that pediatric patients detect SAA when their children have fever. . In the acute phase of viral infection, SAA levels increase significantly, usually between 10 and 100 mg/L, while WBC, CRP, and PCT generally do not increase significantly. Studies have shown that in patients with viral infections, the area under the ROC curve from large to small is SAA>PCT>WBC>CRP (specific values are 0.859, 0.701, 0.700, 0.696). It can be seen that SAA has good diagnostic accuracy for viral infections. . In addition, it should be noted that the joint diagnosis of SAA and CRP is used to judge the disease cycle. Generally, patients with respiratory virus infections usually develop clinical symptoms 36 to 48 hours after infection, while SAA gradually increases after viral infection, and the rise time is earlier than that of CRP. And it is very significant, reaching the peak on the 3rd to 4th day, which is an indicator for distinguishing bacterial infection from viral infection. During the recovery period of the disease, SAA continued to decline, and its decline rate was faster than that of CRP. Therefore, it is recommended to test both at the same time to determine the time of infection. For SAA to assist in the diagnosis of viral infection, it is recommended to dynamically observe the changes in SAA levels and retest every 12 to 24 hours. If the SAA level continues to be higher than 10 mg/L and lower than 100 mg/L, viral infection is likely.
★Application in bacterial infections: Different types of bacterial infections can cause an increase in SAA levels in the body. There is no significant difference in SAA levels between Gram-positive and Gram-negative bacterial infections. In studies comparing bacterial and viral infections at the same site (such as meningitis, diarrhea, etc.), the increase in SAA levels in bacterial infections is higher than that in viral infections. Up to 100~1000mg/L. Special attention is paid to the significant increase in SAA in patients with sepsis, while SAA has a high diagnostic value in patients with neonatal sepsis, with specificity and sensitivity as high as 95% and 82% respectively, compared with CRP and PCT. , diagnostic specificity SAA>CRP>PCT, diagnostic sensitivity PCT>SAA>CRP, therefore, the level of SAA in the acute phase of bacterial infection is significantly higher than that in the acute phase of viral infection, and the SAA level continues to be higher than 100mg/L for the acute phase of bacterial infection. It has a strong suggestive effect. SAA has a high negative predictive value for the diagnosis of neonatal sepsis (this is one of the reasons why it is recommended that SAA be used in pediatrics to diagnose and monitor infectious diseases).
★Application in other infections: The increase in SAA in fungal infections (Candida) is similar to or even higher than in bacterial infections, while CRP does not increase significantly. During Mycoplasma pneumoniae infection, SAA also increased significantly, with an increase of up to 100 mg/L, which was 7.24 times that of CRP. In Kawasaki disease, SAA increases at a high level, reaching an average of 514mg/L, which is 6.31 times higher than CRP. Therefore, SAA and other inflammatory indicators need to be used in conjunction with clinical information to distinguish infections from other pathogens such as fungi and mycoplasma.
★Judgment of disease severity and prognosis: In clinical practice, SAA mainly participates in the inflammatory response in the acute phase and does not play a role in chronic infection (for example, in studies of patients with chronic hepatitis B and hepatitis C, SAA concentrations are at normal levels). For patients in the acute phase of influenza A some time ago, their SAA levels increased significantly, and some severe patients could exceed 500mg/L or even higher. The SAA of patients in the recovery period dropped below 100mg/L. For lower respiratory tract infections caused by viruses, SAA levels in severe patients were significantly higher than those in the mild group, and patients with decreased SAA had a good prognosis. SAA can be elevated to 20 times the normal level in patients with hand, foot and mouth disease, and even up to 1,000 times in severe patients. Therefore, SAA can be used as an independent factor to judge the severity of bacterial, viral and other infectious diseases and inflammation. A level greater than 500 mg/L indicates a serious condition. In terms of prognosis assessment, a 30% decrease after 24 hours of antibiotic treatment can be used to judge that the treatment is effective. The degree of decrease The larger it is, the better the prognosis is.
★Role in non-infectious diseases: SAA will also increase in infectious diseases, such as rheumatoid arthritis, obesity, type 2 diabetes, atherosclerosis, chronic respiratory diseases, tumors, Crohn's disease and Amyloidosis needs to be dialectical in clinical practice. This is also the way in which all inflammatory indicators are used. The dialectical use of inflammatory indicators allows "them" to play their strengths and abandon their shortcomings.
PART03: About joint diagnosis of SAA
★When using SAA, you need to pay attention not only to its own suggestive value, but also to its joint diagnosis with other inflammatory markers. This is also one of the reasons why there are so many inflammatory markers.
★Combined diagnosis of SAA and CRP: The joint diagnosis of SAA and CRP is the most common (both can obtain results on one instrument), which is very helpful in distinguishing bacterial infection and viral infection. In the acute stage of viral infection, , the SAA level increased significantly, but the increase in CRP was not obvious; in the acute stage of bacterial infection, both CRP and SAA will increase significantly, and the increase in SAA is higher than that of CRP, so the combination of CRP and SAA is used Application can help early identification of viral or bacterial infections, facilitate more reasonable anti-infective treatment for patients, and effectively improve patient prognosis.