“Infection indicator” - serum amyloid A (SAA)

Author: Yang Qunsong, Chen Wendong

SAA (serum amyloid A) is an acute phase protein encoded by multiple genes. It is the precursor of tissue amyloid A. It is mainly synthesized by the liver and has a high affinity with high-density lipoprotein (HDL). The SAA in routine testing is A-SAA.

1. Synthesis and Metabolism Pathways

2. Features

The normal human serum SAA content is less than 10mg/L. It begins to increase 3-6 hours after infection, and the increase can reach 10-1000 times the normal value. It is a sensitive indicator reflecting the infection status and inflammation recovery. SAA degradation products can be deposited in different organs in the form of amyloid fibrils. The content is increased in the serum of patients with chronic inflammatory diseases, and it is a new indicator for the diagnosis of such diseases.

3. Clinical significance

At present, the application value of SAA in the early diagnosis, risk assessment, efficacy observation and prognosis evaluation of infectious diseases has been widely recognized; studies in recent years have found that elevated SAA levels have been detected in the serum of patients with non-infectious diseases such as type 2 diabetes, atherosclerosis, tumors, rheumatoid arthritis, transplant rejection, amyloidosis, etc., which has guiding significance for the auxiliary diagnosis of the disease.

IV. Clinical Application Scenarios

(1) Application of combined detection of SAA, CRP and PCT in infectious diseases:

SAA, CRP and PCT are all non-specific infection indicators. Their biological characteristics and clinical application features are summarized in the following table.

In recent years, the combined use of SAA, CRP and PCT has been widely accepted and used in the diagnosis and treatment of infectious diseases. The combined use of the three will have a higher diagnostic efficiency, which can help clinicians determine the type of infectious disease in patients more quickly and accurately, guide clinical medication and avoid abuse of antibiotics. The distribution of clinical departments and disease types for the combined use of SAA, CRP and PCT is shown in the following table.

(2) The “new three routines” for infectious diagnosis in infants and young children: WBC+CRP+SAA

The concept of the “new three routines” was proposed by Professor Jiang Jinjin of the Department of Pediatrics of Changhai Hospital Affiliated to the Second Military Medical University in an academic forum in view of the clinical value of SAA testing in the diagnosis of infectious diseases in infants and young children. A large number of research papers have shown [1-5] that SAA is more significantly elevated in the acute phase of bacterial and viral infections in infants and young children, such as acute bacterial pneumonia, measles, chickenpox, mumps, viral meningitis, and hand, foot and mouth disease, compared with CRP. SAA is significantly elevated in the early stages of neonatal sepsis [6] and has a high diagnostic value. In addition, SAA continues to decline during the recovery phase of the disease, and the rate of decline is faster than that of CRP [7]. It is generally believed that CRP is only sensitive to bacterial infections, while SAA is sensitive to both bacterial and viral infections; SAA is more sensitive than CRP in early infections, rises earlier, and declines faster and to a greater extent during recovery. For outpatients, especially infants and young children, it is necessary to diagnose the disease as quickly and accurately as possible to relieve symptoms and control the progression of the disease. SAA is included as a new indicator in routine testing for infants and young children. It can effectively make up for the shortcomings of routine blood test + CRP in monitoring viral infection, infection severity, treatment effect, and disease progression, accelerate disease diagnosis and treatment, reduce unnecessary use of antibiotics, and benefit the healthy growth of children.

(3) Prediction of cardiovascular event risk by SAA combined with hsCRP

hsCRP is mainly used to assess the risk of coronary heart disease in the primary prevention of cardiovascular disease. The increase in hsCRP reflects the presence of a low-grade inflammatory process and the shedding of atherosclerotic plaques in atherosclerosis. The risk of myocardial infarction in patients with atherosclerosis with high levels of hsCRP is much higher than that in patients with normal levels. When the body is in the acute inflammatory phase, liver cells produce a large amount of SAA. After it is released into the blood, SAA has a high affinity with high-density lipoprotein (HDL), which can replace apoA1 and bind to HDL, resulting in an increase in HDL density, converting HDL from a lipoprotein that protects blood vessels to one that promotes atherosclerosis. Increased concentrations of SAA and hsCRP are positively correlated with the possibility of predicting the risk of cardiovascular events in the future in healthy people. The combined use of the two indicators has a more significant diagnostic value in predicting the risk of cardiovascular events.

(4) Application of SAA in other diseases

SAA is a highly sensitive acute phase protein and can be used as a marker for early diagnosis of transplant rejection. As a precursor of tissue amyloid A (AA), SAA maintains a high concentration level in the serum of almost all patients with AA type (reactive) amyloidosis for a long time, which can provide a more accurate reference for the diagnosis, treatment and prognosis of the disease. In addition, some prospective studies believe that SAA may also be involved in the occurrence and development of diseases such as diabetes, chronic obstructive pulmonary disease, and tumors, and can be used as a research biomarker.

References:

[1]Whicher JT, Chambers RE, Higginson J, et al. Acute phase response of serumamyloid A protein and C reactive protein to the common cold and influenza[J]. JClin Path, 1985, 38(3): 312-316. DOI: 10.1136/jcp.38.3.312.

[2]Ahout IML, Brand KH, Zomer A, et al. Prospective observational study in twoDutch hospitals to assess the performance of inflammatory plasma markers to determine disease severity of viral respiratory tract infections in children[J]. BMJ Open, 2017, 7(6): e014596. DOI: 10.1136/bmjopen-2016-014596.

[3]Nakayama T, Sonoda S, Urano T, et al. Monitoring both serum amyloid protein Aand C-reactive protein as inflammatory markers in infectious diseases[J]. ClinChem, 1993, 39(2): 293-297.DOI: 10.1103/PhysRevE.91.042310.

[4] Zhao Xinfeng, Wu Yidong, Gao Yang, et al. Diagnostic value of serum amyloid A combined with C-reactive protein in children with hand, foot and mouth disease[J]. Chinese Journal of Infectious Diseases, 2016, 34(7): 419-421. DOI:10.3760/cma. j. issn. 1000-6680. 2016.07.007.

[5]Liu J, Huang P, He Y, et al. Serum amyloid A and clusterin as potentialpredictive biomarkers for severe hand, foot and mouth disease by 2D-DIGEproteomics analysis.[J]. Plos One, 2014, 9(9):e108816. DOI:10.1371/journal.pone.0108816.

[6]ChauhanN, Tiwari S, Jain U. Potential biomarkers for effective screening of neonatal sepsis infections: An overview[J]. Microb Pathog, 2017, 107: 234⁃242. DOI: 10.1016/j.micpath.2017.03.042.

[7]FuY, Chen J, Cai B, et al. The use of PCT, CRP, IL-6 and SAA in critically illpatients for an early distinction between candidemia and Gram positive /negative bacteremia[J]. J Infect, 2012, 64(4):438-440. DOI:10.1016/j.jinf.2011.12.019.