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      Distribution of serum amyloid A and establishment of reference intervals in healthy adults

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          Abstract

          Background

          Serum amyloid A (SAA) plays a critical role in acute or chronic and is used in clinical laboratories as an indicator of inflammation. The elevated SAA is closely related to inflammation‐mediated diseases, such as liver diseases, autoimmune diseases, metabolism‐related diseases, amyloidosis, and tumors. However, there is no unified population reference interval for SAA. This study aimed to investigate the distribution of SAA in healthy Chinese adults 20‐79 years of age and to establish its population reference interval.

          Methods

          A total of 2365 healthy subjects met the requirements of this study. The levels of SAA were detected using an AU5821 automatic biochemical analyzer and its original reagents. According to the recommended methods of CLSI C28‐A3 and WS/T 402‐2012, the population reference interval of SAA was established using the unilateral 95th percentile (P 95), and the 90% confidence interval of upper limits was calculated.

          Results

          The distributions of SAA levels were not significantly different between sexes ( P> .05) and also did not differ by age ( P> .05). Therefore, the population reference interval for SAA was established as an upper limit of 11.0 mg/L (90% confidence interval: 9.3‐12.3 mg/L) by using the method of latex immunoturbidimetry.

          Conclusions

          Serum amyloid A is closely related to the occurrence and progression of various diseases. The preliminary establishment of a population reference interval for SAA can fully exert its potential clinical value.

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          Most cited references23

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          Acute phase reactant serum amyloid A in inflammation and other diseases.

          Acute-phase reactant serum amyloid A (A-SAA) plays an important role in acute and chronic inflammation and is used in clinical laboratories as an indicator of inflammation. Although both A-SAA and C-reactive protein (CRP) are acute-phase proteins, the detection of A-SAA is more conclusive than the detection of CRP in patients with viral infections, severe acute pancreatitis, and rejection reactions to kidney transplants. A-SAA has greater clinical diagnostic value in patients who are immunosuppressed, patients with cystic fibrosis who are treated with corticoids, and preterm infants with late-onset sepsis. Nevertheless, for the assessment of the inflammation status and identification of viral infection in other pathologies, such as bacterial infections, the combinatorial use of A-SAA and other acute-phase proteins (APPs), such as CRP and procalcitonin (PCT), can provide more information and sensitivity than the use of any of these proteins alone, and the information generated is important in guiding antibiotic therapy. In addition, A-SAA-associated diseases and the diagnostic value of A-SAA are discussed. However, the relationship between different A-SAA isotypes and their human diseases are mostly derived from research laboratories with limited clinical samples. Thus, further clinical evaluations are necessary to confirm the clinical significance of each A-SAA isotype. Furthermore, the currently available A-SAA assays are based on polyclonal antibodies, which lack isotype specificity and are associated with many inflammatory diseases. Therefore, these assays are usually used in combination with other biomarkers in the clinic.
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            Immune functions of serum amyloid A.

            Serum amyloid A (SAA) is a highly conserved, acute-phase protein synthesized predominantly by the liver. After secretion into the circulation, it associates with high-density lipoprotein (HDL) particles. During acute inflammation, serum SAA levels may rise up to 1000-fold, and under these conditions, SAA displaces apolipoprotein A-I from HDL, thus becoming the major apolipoprotein of circulating HDL3. SAA exhibits significant immunological activity by, for example, inducing the synthesis of several cytokines and by being chemotactic for neutrophils and mast cells. It exerts many of its immunological activities by binding and activating cell-surface receptors, including Toll-like receptor (TLR) 2 and TLR4, formyl peptide receptor-like 1 (FPRL1), class B scavenger receptor CD36, and the ATP receptor P2X7. SAA also recently has been shown to activate the inflammasome cascade, which has a key role in immune activation, thus further stressing the unique role of SAA in immunomodulation. Traditionally, SAA has been considered to have a key role in the pathogenesis of amyloid A-type amyloidosis, but we now understand that it may also participate in the pathogenesis of chronic inflammatory diseases, such as rheumatoid arthritis and atherosclerosis. Thus, SAA is one potential target in the treatment of diseases associated with chronic inflammation. The purpose of this review is to shed light on SAA as an immunologically active protein. We also focus on the recent findings implicating SAA in the regulation of the inflammasome cascade.
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              Acute phase protein response to viral infection and vaccination

              Organisms respond in multiple ways to microbial infections. Pathogen invasion tipically triggers an inflammatory response where acute phase proteins (APP) have a key role. Pentraxins (PTX) are a family of highly conserved APP that play a part in the host defense against infection. The larger proteins of the family are simply named pentraxins, while c-reactive proteins (CRP) and serum amyloid proteins (SAA, SAP) are known as short pentraxins. Although high APP levels have been broadly associated with bacterial infections, there is a growing body of evidence revealing increased PTX, CRP and SAP expression upon viral infection. Furthermore, CRP, PTX and SAP have shown their potential as diagnostic markers and predictors of disease outcome. Likewise, the measurement of APP levels can be valuable to determine the efficacy of antiviral therapies and vaccines. From the practical point of view, the ability of APP to reduce viral infectivity has been observed in several virus-host models. This has prompted investigation efforts to assess the role of acute phase response proteins as immunoregulatory molecules and their potential as therapeutic reagents. This work aims to present an overview of the APP response to viral infections reviewing the current knowledge in the field.
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                Author and article information

                Contributors
                yfm31095018@163.com
                Journal
                J Clin Lab Anal
                J. Clin. Lab. Anal
                10.1002/(ISSN)1098-2825
                JCLA
                Journal of Clinical Laboratory Analysis
                John Wiley and Sons Inc. (Hoboken )
                0887-8013
                1098-2825
                13 November 2019
                April 2020
                : 34
                : 4 ( doiID: 10.1002/jcla.v34.4 )
                : e23120
                Affiliations
                [ 1 ] Department of Laboratory Medicine The Second People's Hospital of Lianyungang Lianyungang China
                [ 2 ] Department of Endocrinology The Second People's Hospital of Lianyungang Lianyungang China
                Author notes
                [*] [* ] Correspondence

                Fumeng Yang, Department of Laboratory Medicine, The Second People's Hospital of Lianyungang, Lianyungang, China.

                Email: yfm31095018@ 123456163.com

                Author information
                https://orcid.org/0000-0002-2636-7340
                Article
                JCLA23120
                10.1002/jcla.23120
                7171307
                31724213
                3f38d6be-fc7a-40c7-9448-811e8a0471ee
                © 2019 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 September 2019
                : 22 October 2019
                : 29 October 2019
                Page count
                Figures: 2, Tables: 3, Pages: 6, Words: 4058
                Funding
                Funded by: the Young and Middle‐aged Talents Growth Foundation of the Second People's Hospital of Lianyungang
                Award ID: TQ201710
                Funded by: Research funding was from the Bengbu Medical College
                Award ID: BYKY17184, 18178
                Funded by: he Health Scientific Research Project in Lianyungang
                Award ID: 201721, 201817
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                April 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.1 mode:remove_FC converted:21.04.2020

                Clinical chemistry
                acute‐phase reactive protein,reference interval,serum amyloid a
                Clinical chemistry
                acute‐phase reactive protein, reference interval, serum amyloid a

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