Introduction
The first reaction of the body to immunological stress is the innate, nonspecific response preceding specific immune responses. The Acute Phase Response (APR) is a major early complex systemic defense mechanism of the organism which is triggered in response to either local or systemic disturbances caused by infection, inflammation or immunological disorders, neoplastic disorders, stress, tissue injury due to trauma or surgery [1,2].
The term “acute phase response” (APR) refers to a systematic nonspecific and complex reaction caused by an organism’s innate body defense that is initiated immediately after any tissue damage, such as infection, trauma, neoplasia, inflammation, and stress [3]. This response is marked by the expression of certain blood proteins which are termed as APPs. These APPs are components of the nonspecific innate immune response pathway and their plasma concentration is proportional to the extent of tissue damage [3,4].
The serum concentrations of APP increase or decrease by at least 25% or more during inflammation. Such proteins are called either positive, which show an upregulated serum concentration, e.g., C-reactive proteins, Serum Amyloid A & Fibrinogen or negative APP, which show a downregulated serum concentration, e.g., Albumin, Transferrin in response to inflammation [5-7]. Positive APPs are categorised as major, moderate and minor or negative depending on the magnitude of increase: A 10-100 fold increase is seen with major APPs, while an increase of 2 to 10 fold is seen with moderate APPs and whereas a slight increase was seen with minor APPs [3,8].
Recently the measurement of APP serum levels is used as a laboratory; diagnostic and prognostic marker of the intensity of the inflammatory process in various diseases [5-7].
Serum Amyloid A Protein
Serum Amyloid A (SAA) proteins are small APPs (104 amino acids) that are elevated under inflammatory conditions like trauma, infection, late-stage malignancy and severe stress as much as 1000-fold in 24 hours. Viral infections such as SARS2 can lead to inflammation and rapid viral replication. Thus, consequently leading to the release of an array of proinflammatory cytokines [9-12]. A recent study showed SAA to have the potential of being an independent predictive factor of COVID-19 [9]. It is also expressed in sterile inflammatory conditions and acts as a mediator of danger signal in inflammation [13,14]. SAA is an high-density apolipoprotein and is primarily formed in the liver in large quantities on induction by systemic infection and in the intestine by bacterial colonisation [15,16]. It is expressed by a variety of human cells including hepatocytes, adipocytes, macrophages, and fibroblast-like synoviocytes [17]. In addition, it is also associated with High-Density Lipoproteins (HDL) in plasma [18]. SAA proteins were first isolated and named five decades ago [12].
Functions of Serum Amyloid A Protein
SAA participates as an APP in lipid metabolism by influencing HDL-cholesterol transport [19]. In tissues, it attracts inflammatory cells and acts as an effector of neutrophil functions and modulates immune response [20]. Moreover, SAA induces synthesis of several cytokines and is chemotactic to neutrophils, monocytes and mast cells. It has also been recently shown to activate the inflammasome cascade and therefore, has a significant role in immunomodulation [21-24]. Summary of functions of Serum Amyloid A protein are listed in [Table/Fig-1].
Functions of Serum Amyloid A Protein [12,19,20,22-30].
| Author, Reference, Year | Role of Serum Amyloid A protein |
|---|
| Badolata R et al., [23]:1994, Su SB et al., [24]:1999 | Phagocyte migrationNeutrophil migrationMonocyte migration. |
| Banka CL et al., [19]:1995 | Is LipophilicParticipates in Lipid MetabolismCholesterol efflux.Displace apo-A1. |
| Olsson N et al., [22]:1999 | Induces Chemotaxis of Human Mast Cells |
| Hatanaka E et al., [20]:2003 | Neutrophil priming. |
| Shah C et al., [25]:2006 | Innate opsonin.Opsonizes gram-negative bacteria;Induced bacterial clearance |
| Su SB et al., [24]:1994, El Kebir D et al., [26]:2007 | Promotes PMN adhesion to endothelial cellsExtends the lifespan of PMN cells.Suppressing neutrophil apoptosis. |
| Sandri S et al., [27]:2008 | Induces nitric oxide production through TLR4 in human macrophages |
| de Buck M et al., [28]: 2016 | Inflammatory cytokine expression.Cytokine and chemokine-inducing capacity.Activates transcription factors. |
| Yan Q et al., [29]:2014, Li et al., [30]:2017 | Epigenetic regulation of proinflammatory cytokine gene expression. |
| Sack Jr GH [12]:2018 | Cytokine-like protein/Helps in cell to cell communication.Provides feedback in inflammatory, immunologic, neoplastic and protective pathways. |
Role of Serum Amyloid A Protein and its Association with Various Diseases
The biology of SAA since its first identification decades ago was not understood well. SAA, in cases of Amyloidosis, gets deposited extracellularly as insoluble amyloid fibrils that cause damage to the tissue structure and disrupt function. A 19th century pathologists who conducted light microscope postmortem examinations found amorphous infiltrative changes in organs such as kidney, liver and heart. They considered this material to be carbohydrate and of plant origin and the term ‘amyloid’ originated [12,31]. However, it is now well understood that SAA has a potent proinflammatory role. Its serum levels rise with many inflammatory and disease conditions and may have a role in pathogenesis of a number of diseases. Thus, SAA can serve to be a potential target in the treatment of diseases associated with chronic inflammation [21]. [Table/Fig-2] summarises the roles of Serum Amyloid A Protein in the pathogenesis of various diseases.
Role of Serum Amyloid A Protein in the pathogenesis of various diseases [32-56].
| Author, Reference, Year | Pathogenesis | Disease |
|---|
| Chambers RE et al., [32]:1987, Niederau C et al., [33]:1997 | Acute phase marker | Crohn’s disease |
| Liuzzo G et al., [34]:1994 | Important inflammatory component in pathogenesis.Elevation of CRP and SAA predicts poor outcome. | Severe unstable angina |
| Ristori G et al., [35]:1998, Chung TF et al., [36]: 2000Yokote H et al., [37]:2013 | Elevated SAA levels.Peripheral inflammation.SAA plays a role in neuronal loss and white matter damage. | Multiple sclerosis. |
| Chung TF et al., [36]:2000 | SAA can inhibit Lipid synthesis.SAA plays a role in neuronal loss and white matter damage. | Alzheimer disease |
| Niemi K et al., [38]:2006 | Degradation of SAA and formation of Amyloidogenic SAA Fragment. | Amyloidosis |
| Engin-Ustün Y et al., [39]:2007, Ibrahim MI et al., [40]:2017 Swidan KH et al., [41]:2020, | Elevated levels of Acute phase proteins including SAA.May at least in part contribute to the pathogenesis of pre-eclampsia. | Pre-Eclampsia |
| Deguchi I et al., [42]:2010, Shridas P and Tannock LR [43]:2019, Fernández JA et al., [44]:2020. | Elevation of SAA is strongly linked to venous thromboembolic diseaseSAA itself is a potential enhancer of thrombin generation. | Thrombosis |
| Zhao Y et al., [45]:2010 | Proinflammatory.Insulin resistance. | Obesity |
| Marzi C et al., [46]:2013, Klüppelholz B [47]:2015 | Elevated SAA were associated with early deterioration of glycaemia.Strong prospective associations with type 2 diabetes.Proinflammatory. | Diabetes |
| Biaoxue R et al., [48]:2016 | Higher levels of SAA are seen in patients with lung cancer and can be correlated with relatively high specificity with occurrence and development of lung cancer.SAA could be a new biomarker-diagnostic and prognostic indicator for some malignant tumors. | Neoplasia |
| Getz GS et al., [49]:2016, Shridas P and Tannock LR [43]: 2019 | SAA participates in the early atherogenic process and pro-atherogenic activity.It is a plasma biomarker for future cardiovascular events | Atherosclerosis |
| Vitale A et al., [50]: 2014, Agilli M et al., [51]:2016, Lopalco G et al., [52]:2015 | SAA levels may identify a thrombotic risk.Studies suggest the existence of a relationship between SAA and proinflammatory cytokines in the intricate scenario of BD pathogenesis. | Behçet’s Disease |
| Morizane S et al., [53]:2016, Couderc E et al., [54]:2017 | SAA contributes to pathogenesis. | Psoriasis |
| Lu W et al., [55]:2019 | SAA is synthesised in the liver by activated monocytes and macrophages in response to pro-inflammatory cytokines. | Acute and Chronic Urticaria. |
| Yuan ZY et al., [56]:2019 | Elevated serum SAA levels are seen in all patients with active liver diseases.Sensitive biomarker in pyogenic liver abscess. | Pyogenic liver abscess |
Circulating Serum Amyloid A Protein Concentrations
Previous studies have shown that physiological SAA serum levels vary substantially [57-60]. In healthy individuals, the serum concentration of SAA is about 1-2 μg/mL, that is, (100-200 ng/mL) [61]. However, some authors found relatively high physiological levels of SAA (15-40 μg/mL) [62]. This discrepancy may be the result of subclinical infection or inflammation [62].
The comparison between SAA levels in serum levels in health and disease showed an increase in SAA concentration during various diseases; inflammatory, autoimmune, neoplastic, trauma, surgery and other diseases. In disease, serum SAA levels vary between studies, ranging from about 10 μg/mL to about 500 μg/mL, up to even 1 mg/mL. In general, we can state that under pathological conditions, SAA concentrations raise more than 10 μg/mL and up to 1 mg/mL [63-66]. Therefore, serum SAA concentration is very sensitive but is generally a nonspecific marker in diagnosis, prognosis and monitoring of inflammatory, infectious diseases and cancer [67].
Serum Amyloid A in Periodontal Inflammation
Periodontitis is a chronic polymicrobial disease exaggerated by self-damaging host immune response elicited by bacterial colonisation as biofilms [68,69]. SAA concentrations in serum and gingival crevicular fluid in patients with chronic periodontitis is comparably elevated to periodontally healthy individuals [70,71]. It was found that high serum titers of antibodies to P. gingivalis and the presence of periodontal inflammation were independently related to high SAA and hs-CRP levels [70]. Vuletic S et al., in a study in 66 patients with advanced periodontal disease, showed that full-mouth tooth extraction significantly reduced SAA, a marker of inflammation [72]. Ardila CM et al., showed that pathological levels of SAA were associated with periodontal disease [70,73]. A recent study by Song LT et al., showed that inflammatory gingival tissues express SAA strongly. This can set in motion the secretion of inflammatory cytokines such as IL-6 and IL-8 by the TLR-2 pathway (Toll-like receptors) in human gingival fibroblasts. Thereby, the SAA participates in periodontal inflammation and the pathogenesis of chronic periodontitis [74].
Serum Amyloid A in Periapical Inflammation
The understanding of periapical inflammation in relation to bacterial infection has led to several studies on host-bacteria interactions [75-77]. Endodontic infection has shown to activate a series of inflammatory events which contributes to the containment and killing of pathogens. This systemic reaction to local disturbances in its homeostasis caused by infection is considered as APR. Thus, inflammation is primarily a protective mechanism in an individual. However, a chronic inflammatory state may result in failure of bacterial clearance, leading to periapical tissue destruction [1,78-80].
Currently, the factors which are considered crucial for induction of innate immune responses are bacterial infection, Pathogen-Associated Molecular Patterns (PAMPs) and Damage Associated Molecular Patterns (DAMPs) [75].
The host defence activation by pathogens depends on specific recognition of PAMPs which are detected through Pattern Recognition Receptors (PRRs) [81,82] These include TLR and Nucleotide Binding Site/Leucine Rich Repeat (NBS/LRR) [83,84]. The DAMPs are the endogenous molecules which are released by damaged or necrotic host cells [85,86]. Investigations have identified several DAMPs, and their number is still increasing [87,88]. The macrophages recognises DAMPs and inflammatory responses are triggered through different ways including inflammasomes and TLRs [88,89].
The DAMPs have shown to originate from various sources like plasma proteins (such as Serum Amyloid A), extracellular proteins (like Biglycan) and intracellular proteins (such as high mobility group box1) [13,88,90-92]. The plasma proteins including SAA have shown to extravasate from vessels to the sites of inflammation and act as DAMPs to produce inflammatory cytokines through TLR4 or TLR2 [13,90-92]. In situations, when DAMP’s are persistently released, inflammation will fail to resolve which will lead to chronic inflammatory diseases, fibrosis or granulation tissue development [86].
A recent study revealed the expression of SAA (a DAMP) locally in the periapical lesions of humans and mice and also found the circulating SAA in mice to elevate in response to endodontic infection [75].
Conclusion(s)
SAA has been shown to regulate innate and adaptive immunity and plays a significant role in the pathogenesis of several diseases. It has also been found that SAA might have a closer role in the pathogenesis of periodontal diseases and chronic periapical inflammation. A thorough understanding of the regulatory mechanism of SAA in chronic periodontitis and chronic periapical inflammation will help to design better treatment modalities for these specific diseases.
[1]. Gruys E, Toussaint MJM, Niewold TA, Koopmans SJ, Acute phase reaction and acute phase proteinsJ Zhejiang Univ Sci B 2005 6(11):1045-56.10.1631/jzus.2005.B104516252337 [Google Scholar] [CrossRef] [PubMed]
[2]. Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, Inflammatory responses and inflammation-associated diseases in organsOncotarget 2018 9(6):7204-18.10.18632/oncotarget.2320829467962 [Google Scholar] [CrossRef] [PubMed]
[3]. Gelain ME, Bonsembiante F, Acute phase proteins in marine mammals: State of art, perspectives and challengesFront Immunol 2019 29(10):122010.3389/fimmu.2019.0122031191557 [Google Scholar] [CrossRef] [PubMed]
[4]. Liu C-C, Ahearn JM, Acute-phase proteins and inflammation: Immunological and clinical implicationsIn: Measuring Immunity 2005 Elsevier:131-43.10.1016/B978-012455900-4/50272-5 [Google Scholar] [CrossRef]
[5]. Pucher B, Sobieska M, Grzegorowski M, Szydlowski J, The acute phase proteins reaction in children suffering from pseudocroupMediators Inflamm 2019 2019:651830810.1155/2019/65183083104902 [Google Scholar] [CrossRef] [PubMed]
[6]. Acute phase proteins | eClinpath [Internet]. eClinpath. [cited 2020 Jul 4]. Available from: http://eclinpath.com/chemistry/proteins/acute-phase-proteins/ [Google Scholar]
[7]. Ackermann MR, Inflammation and Healing1In: Pathologic Basis of Veterinary Disease 2017 Elsevier:73-131.e2.10.1016/B978-0-323-35775-3.00003-528274196 [Google Scholar] [CrossRef] [PubMed]
[8]. Ceron JJ, Eckersall PD, Martýnez-Subiela S, Acute phase proteins in dogs and cats: Current knowledge and future perspectivesVet Clin Pathol 2005 34(2):85-99.10.1111/j.1939-165X.2005.tb00019.x15902658 [Google Scholar] [CrossRef] [PubMed]
[9]. Mo X, Su Z, Lei C, Chen D, Peng H, Chen R, Serum amyloid A is a predictor for prognosis of COVID-19 [Internet]. Vol. 25Respirology 2020 :764-65.Available from: http://dx.doi.org/10.1111/resp.1384010.1111/resp.1384032406576 [Google Scholar] [CrossRef] [PubMed]
[10]. Butler J, Bates D, Serum amylase and acute pancreatitisEmerg Med J 2003 20(6):550-51.10.1136/emj.20.6.55014623849 [Google Scholar] [CrossRef] [PubMed]
[11]. Vege SS, Approach to the patient with elevated serum amylase or lipase [Internet]UpToDate[cited 2019 May 13]. Available from: https://www.uptodate.com/contents/approach-to-the-patient-with-elevated-serum-amylase-or-lipase [Google Scholar]
[12]. Sack GH Jr, Serum amyloid A- A reviewMol Med 2018 24(1):4610.1186/s10020-018-0047-030165816 [Google Scholar] [CrossRef] [PubMed]
[13]. Ye RD, Sun L, Emerging functions of serum amyloid A in inflammation [Internet]. Vol. 98Journal of Leukocyte Biology 2015 :923-29.Available from: http://dx.doi.org/10.1189/jlb.3vmr0315-080r10.1189/jlb.3VMR0315-080R26130702 [Google Scholar] [CrossRef] [PubMed]
[14]. Matzinger P, Friendly and dangerous signals: Is the tissue in control?Nat Immunol 2007 8(1):11-13.10.1038/ni0107-1117179963 [Google Scholar] [CrossRef] [PubMed]
[15]. Hu Z, Bang YJ, Ruhn KA, Hooper LV, Molecular basis for retinol binding by serum amyloid A during infectionProc Natl Acad Sci U S A 2019 116(38):19077-82.10.1073/pnas.191071311631484771 [Google Scholar] [CrossRef] [PubMed]
[16]. Husby G, Marhaug G, Dowtor B, Sletten K, Sipe JD, Serum amyloid A (SAA): Biochemistry, genetics and the pathogenesis of AA amyloidosisAmyloid 1994 1(2):119-37.10.3109/13506129409148635 [Google Scholar] [CrossRef]
[17]. Saxena A, Cronstein BN, Acute Phase Reactants and the Concept of InflammationIn: Kelley’s Textbook of Rheumatology 2013 Elsevier:818-29.e4.10.1016/B978-1-4377-1738-9.00057-8 [Google Scholar] [CrossRef]
[18]. Juul-Madsen HR, Viertlböeck B, Härtle S, Smith AL, Göbel TW, Innate Immune ResponsesIn: Avian Immunology 2014 Elsevier:121-47.10.1016/B978-0-12-396965-1.00007-8 [Google Scholar] [CrossRef]
[19]. Banka CL, Yuan T, de Beer MC, Kindy M, Curtiss LK, de Beer FC, Serum amyloid A (SAA): Influence on HDL-mediated cellular cholesterol effluxJ Lipid Res 1995 36(5):1058-65.10.1016/S0022-2275(20)39863-1 [Google Scholar] [CrossRef]
[20]. Hatanaka E, Pereira Ribeiro F, Campa A, The acute phase protein serum amyloid A primes neutrophilsFEMS Immunol Med Microbiol 2003 38(1):81-84.10.1016/S0928-8244(03)00112-3 [Google Scholar] [CrossRef]
[21]. Eklund KK, Niemi K, Kovanen PT, Immune functions of serum amyloid ACrit Rev Immunol 2012 32(4):335-48.10.1615/CritRevImmunol.v32.i4.4023237509 [Google Scholar] [CrossRef] [PubMed]
[22]. Olsson N, Siegbahn A, Nilsson G, Serum amyloid A induces chemotaxis of human mast cells by activating a pertussis toxin-sensitive signal transduction pathwayBiochem Biophys Res Commun 1999 254(1):143-46.10.1006/bbrc.1998.99119920747 [Google Scholar] [CrossRef] [PubMed]
[23]. Badolato R, Wang JM, Murphy WJ, Lloyd AR, Michiel DF, Bausserman LL, Serum amyloid A is a chemoattractant: Induction of migration, adhesion, and tissue infiltration of monocytes and polymorphonuclear leukocytesJ Exp Med 1994 180(1):203-09.10.1084/jem.180.1.2037516407 [Google Scholar] [CrossRef] [PubMed]
[24]. Su SB, Gong W, Gao JL, Shen W, Murphy PM, Oppenheim JJ, A seven-transmembrane, G protein-coupled receptor, FPRL1, mediates the chemotactic activity of serum amyloid A for human phagocytic cellsJ Exp Med 1999 189(2):395-402.10.1084/jem.189.2.3959892621 [Google Scholar] [CrossRef] [PubMed]
[25]. Shah C, Hari-Dass R, Raynes JG, Serum amyloid A is an innate immune opsonin for Gram-negative bacteriaBlood 2006 108(5):1751-57.10.1182/blood-2005-11-01193216735604 [Google Scholar] [CrossRef] [PubMed]
[26]. El Kebir D, József L, Khreiss T, Pan W, Petasis NA, Serhan CN, Aspirin-triggered lipoxins override the apoptosis-delaying action of serum amyloid A in human neutrophils: A novel mechanism for resolution of inflammationJ Immunol 2007 179(1):616-22.10.4049/jimmunol.179.1.61617579083 [Google Scholar] [CrossRef] [PubMed]
[27]. Sandri S, Rodriguez D, Gomes E, Monteiro HP, Russo M, Campa A, Is serum amyloid A an endogenous TLR4 agonist?J Leukoc Biol 2008 83(5):1174-80.10.1189/jlb.040720318252871 [Google Scholar] [CrossRef] [PubMed]
[28]. De Buck M, Gouwy M, Wang JM, Van Snick J, Proost P, Struyf S, The cytokine-serum amyloid A-chemokine networkCytokine Growth Factor Rev 2016 30:55-69.10.1016/j.cytogfr.2015.12.01026794452 [Google Scholar] [CrossRef] [PubMed]
[29]. Yan Q, Sun L, Zhu Z, Wang L, Li S, Ye RD, Jmjd3-mediated epigenetic regulation of inflammatory cytokine gene expression in serum amyloid A-stimulated macrophagesCell Signal 2014 26(9):1783-91.10.1016/j.cellsig.2014.03.02524703936 [Google Scholar] [CrossRef] [PubMed]
[30]. Li W, Wang W, Zuo R, Liu C, Shu Q, Ying H, Induction of pro-inflammatory genes by serum amyloid A1 in human amnion fibroblastsSci Rep 2017 7(1):69310.1038/s41598-017-00782-928386088 [Google Scholar] [CrossRef] [PubMed]
[31]. Simons JP, Al-Shawi R, Ellmerich S, Speck I, Aslam S, Hutchinson WL, Pathogenetic mechanisms of amyloid A amyloidosisProc Natl Acad Sci U S A 2013 110(40):16115-20.10.1073/pnas.130662111023959890 [Google Scholar] [CrossRef] [PubMed]
[32]. Chambers RE, Stross P, Barry RE, Whicher JT, Serum amyloid A protein compared with C-reactive protein, alpha 1-antichymotrypsin and alpha 1-acid glycoprotein as a monitor of inflammatory bowel diseaseEur J Clin Invest 1987 17(5):460-67.10.1111/j.1365-2362.1987.tb01143.x3121351 [Google Scholar] [CrossRef] [PubMed]
[33]. Niederau C, Backmerhoff F, Schumacher B, Niederau C, Inflammatory mediators and acute phase proteins in patients with Crohn’s disease and ulcerative colitisHepatogastroenterology 1997 44(13):90-107. [Google Scholar]
[34]. Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable anginaN Engl J Med 1994 331(7):417-24.10.1056/NEJM1994081833107017880233 [Google Scholar] [CrossRef] [PubMed]
[35]. Ristori G, Laurenti F, Stacchini P, Gasperini C, Buttinelli C, Pozzilli C, Serum amyloid A protein is elevated in relapsing-remitting multiple sclerosisJ Neuroimmunol 1998 88(1-2):09-12.10.1016/S0165-5728(98)00037-X [Google Scholar] [CrossRef]
[36]. Chung TF, Sipe JD, McKee A, Fine RE, Schreiber BM, Liang JS, Serum amyloid A in Alzheimer’s disease brain is predominantly localized to myelin sheaths and axonal membraneAmyloid 2000 7(2):105-10.10.3109/1350612000914624610842712 [Google Scholar] [CrossRef] [PubMed]
[37]. Yokote H, Yagi Y, Watanabe Y, Amino T, Kamata T, Mizusawa H, Serum amyloid A level is increased in neuromyelitis optica and atypical multiple sclerosis with smaller T2 lesion volume in brain MRIJ Neuroimmunol 2013 259(1-2):92-95.10.1016/j.jneuroim.2013.03.00423566403 [Google Scholar] [CrossRef] [PubMed]
[38]. Niemi K, Baumann MH, Kovanen PT, Eklund KK, Serum amyloid A (SAA) activates human mast cells which leads into degradation of SAA and generation of an amyloidogenic SAA fragmentBiochim Biophys Acta 2006 1762(4):424-30.10.1016/j.bbadis.2006.01.00116483749 [Google Scholar] [CrossRef] [PubMed]
[39]. Engin-Ustün Y, Ustün Y, Karabulut AB, Ozkaplan E, Meydanli MM, Kafkasli A, Serum amyloid A levels are increased in pre-eclampsiaGynecol Obstet Invest 2007 64(2):117-20.10.1159/00010032917339772 [Google Scholar] [CrossRef] [PubMed]
[40]. Ibrahim MI, Ramy AR, Abdelhamid AS, Ellaithy MI, Omar A, Harara RM, Maternal serum amyloid A level as a novel marker of primary unexplained recurrent early pregnancy lossInt J Gynaecol Obstet 2017 136(3):298-303.10.1002/ijgo.1207628099717 [Google Scholar] [CrossRef] [PubMed]
[41]. Swidan KH, Sweed MS, Abbas AM, Jewi MK, Serum Amyloid A in PreeclampsiaQJM: An International Journal of Medicine [Internet] 2020 Mar 1 113(Supplement_1)Available from: https://academic.oup.com/qjmed/article/doi/10.1093/qjmed/hcaa056.022/582926510.1093/qjmed/hcaa056.022 [Google Scholar] [CrossRef]
[42]. Deguchi H, Elias DJ, Navarro S, Espana F, Griffin JH, Plasma serum amyloid A levels are increased in venous thrombosis patients and are correlated with blood coagulabilityBlood 2010 116(21):15510.1182/blood.V116.21.155.155 [Google Scholar] [CrossRef]
[43]. Shridas P, Tannock LR, Role of serum amyloid A in atherosclerosisCurr Opin Lipidol 2019 30(4):320-25.10.1097/MOL.000000000000061631135596 [Google Scholar] [CrossRef] [PubMed]
[44]. Fernández JA, Deguchi H, Elias DJ, Griffin JH, Serum amyloid A4 is a procoagulant apolipoprotein that it is elevated in venous thrombosis patientsRes Pract Thromb Haemost 2020 4(2):217-23.10.1002/rth2.1229132110751 [Google Scholar] [CrossRef] [PubMed]
[45]. Zhao Y, He X, Shi X, Huang C, Liu J, Zhou S, Association between serum amyloid A and obesity: A meta-analysis and systematic reviewInflamm Res 2010 59(5):323-34.10.1007/s00011-010-0163-y20140694 [Google Scholar] [CrossRef] [PubMed]
[46]. Marzi C, Huth C, Herder C, Baumert J, Thorand B, Rathmann W, Acute-phase serum amyloid A protein and its implication in the development of type 2 diabetes in the KORA S4/F4 studyDiabetes Care 2013 36(5):1321-26.10.2337/dc12-151423238662 [Google Scholar] [CrossRef] [PubMed]
[47]. Klüppelholz B, Thorand B, Koenig W, de Las Heras Gala T, Meisinger C, Huth C, Association of subclinical inflammation with deterioration of glycaemia before the diagnosis of type 2 diabetes: The KORA S4/F4 studyDiabetologia 2015 58(10):2269-77.10.1007/s00125-015-3679-426155746 [Google Scholar] [CrossRef] [PubMed]
[48]. Biaoxue R, Hua L, Wenlong G, Shuanying Y, Increased serum amyloid A as potential diagnostic marker for lung cancer: A meta-analysis based on nine studiesBMC Cancer 2016 16(1):83610.1186/s12885-016-2882-027809798 [Google Scholar] [CrossRef] [PubMed]
[49]. Getz GS, Krishack PA, Reardon CA, Serum amyloid A and atherosclerosisCurr Opin Lipidol 2016 27(5):531-35.10.1097/MOL.000000000000033127579547 [Google Scholar] [CrossRef] [PubMed]
[50]. Vitale A, Rigante D, Lopalco G, Brizi MG, Caso F, Franceschini R, Serum amyloid-A in Behçet’s diseaseClin Rheumatol 2014 33(8):1165-67.10.1007/s10067-014-2555-924659331 [Google Scholar] [CrossRef] [PubMed]
[51]. Agilli M, Aydin FN, Kurt YG, Cayci T, Importance of serum amyloid-A in Behçet’s diseaseClin Rheumatol 2016 35(2):551-52.10.1007/s10067-014-2860-325586523 [Google Scholar] [CrossRef] [PubMed]
[52]. Lopalco G, Lucherini OM, Vitale A, Talarico R, Lopalco A, Galeazzi M, Putative Role of Serum Amyloid-A and Proinflammatory Cytokines as Biomarkers for Behcet’s DiseaseMedicine 2015 94(42):e185810.1097/MD.000000000000185826496336 [Google Scholar] [CrossRef] [PubMed]
[53]. Morizane S, Takiguchi T, Tenta A, Mizuno K, Iwatsuki K, Skin inflammation through innate immunity contributes to the elevation of serum amyloid A protein level of psoriatic patientsJ Dermatol Sci 2016 84(1):e7210.1016/j.jdermsci.2016.08.222 [Google Scholar] [CrossRef]
[54]. Couderc E, Morel F, Levillain P, Buffière-Morgado A, Camus M, Paquier C, Interleukin-17A-induced production of acute serum amyloid A by keratinocytes contributes to psoriasis pathogenesisPLoS One 2017 12(7):e018148610.1371/journal.pone.018148628708859 [Google Scholar] [CrossRef] [PubMed]
[55]. Lu W, Chen B, Wang C, Yang X, Zhou C, Serum amyloid A levels in acute and chronic urticariaAn Bras Dermatol 2014 94(4):411-15.10.1590/abd1806-4841.2019776131644612 [Google Scholar] [CrossRef] [PubMed]
[56]. Yuan ZY, Zhang XX, Wu YJ, Zeng ZP, She WM, Chen SY, Serum amyloid A levels in patients with liver diseasesWorld J Gastroenterol 2019 25(43):6440-50.10.3748/wjg.v25.i43.644031798280 [Google Scholar] [CrossRef] [PubMed]
[57]. Melzi d’Eril G, Anesi A, Maggiore M, Leoni V, Biological variation of serum amyloid A in healthy subjectsClin Chem 2001 47(8):1498-99.10.1093/clinchem/47.8.1498 [Google Scholar] [CrossRef]
[58]. De Buck M, Gouwy M, Wang JM, Van Snick J, Opdenakker G, Struyf S, Structure and expression of different Serum Amyloid A (SAA) Variants and their concentration-dependent functions during host insultsCurr Med Chem 2016 23(17):1725-55.10.2174/092986732366616041811460027087246 [Google Scholar] [CrossRef] [PubMed]
[59]. Wang JY, Zheng YZ, Yang J, Lin YH, Dai SQ, Zhang G, Elevated levels of serum amyloid A indicate poor prognosis in patients with esophageal squamous cell carcinomaBMC Cancer 2012 12:36510.1186/1471-2407-12-36522917173 [Google Scholar] [CrossRef] [PubMed]
[60]. Rho YH, Chung CP, Oeser A, Solus J, Asanuma Y, Sokka T, Inflammatory mediators and premature coronary atherosclerosis in rheumatoid arthritisArthritis Rheum 2009 61(11):1580-85.10.1002/art.2500919877084 [Google Scholar] [CrossRef] [PubMed]
[61]. Shainkin-Kestenbaum R, Winikoff Y, Cristal N, Serum amyloid A concentrations during the course of acute ischaemic heart diseaseJ Clin Pathol 1986 39(6):635-37.10.1136/jcp.39.6.6353722415 [Google Scholar] [CrossRef] [PubMed]
[62]. Sung HJ, Ahn JM, Yoon YH, Rhim TY, Park CS, Park JY, Identification and validation of SAA as a potential lung cancer biomarker and its involvement in metastatic pathogenesis of lung cancerJ Proteome Res 2011 10(3):1383-95.10.1021/pr101154j21141971 [Google Scholar] [CrossRef] [PubMed]
[63]. Urieli-Shoval S, Finci-Yeheskel Z, Dishon S, Galinsky D, Linke RP, Ariel I, Expression of serum amyloid a in human ovarian epithelial tumors: Implication for a role in ovarian tumorigenesisJ Histochem Cytochem 2010 58(11):1015-23.10.1369/jhc.2010.95682120713982 [Google Scholar] [CrossRef] [PubMed]
[64]. Cocco E, Bellone S, El-Sahwi K, Cargnelutti M, Casagrande F, Buza N, Serum amyloid A (SAA): A novel biomarker for uterine serous papillary cancerBr J Cancer 2009 101(2):335-41.10.1038/sj.bjc.660512919536090 [Google Scholar] [CrossRef] [PubMed]
[65]. Targońska-Stępniak B, Majdan M, Serum amyloid A as a marker of persistent inflammation and an indicator of cardiovascular and renal involvement in patients with rheumatoid arthritisMediators Inflamm 2014 2014:79362810.1155/2014/79362825525305 [Google Scholar] [CrossRef] [PubMed]
[66]. Cocco E, Bellone S, El-Sahwi K, Cargnelutti M, Buza N, Tavassoli FA, Serum amyloid A: A novel biomarker for endometrial cancerCancer 2010 116(4):843-51.10.1002/cncr.2483820041483 [Google Scholar] [CrossRef] [PubMed]
[67]. Marhaug G, Dowton SB, Serum amyloid A: An acute phase apolipoprotein and precursor of AA amyloidBaillieres Clin Rheumatol 1994 8(3):553-73.10.1016/S0950-3579(05)80115-3 [Google Scholar] [CrossRef]
[68]. Ebersole JL, Dawson D 3rd, Emecen-Huja P, Nagarajan R, Howard K, Grady ME, The periodontal war: Microbes and immunityPeriodontol 2000 2017 75(1):52-115.10.1111/prd.1222228758303 [Google Scholar] [CrossRef] [PubMed]
[69]. Silva N, Abusleme L, Bravo D, Dutzan N, Garcia-Sesnich J, Vernal R, Host response mechanisms in periodontal diseasesJ Appl Oral Sci 2015 23(3):329-55.10.1590/1678-77572014025926221929 [Google Scholar] [CrossRef] [PubMed]
[70]. Ardila CM, Guzmán IC, Comparison of serum amyloid A protein and C-reactive protein levels as inflammatory markers in periodontitis [Internet]. Vol. 45Journal of Periodontal & Implant Science 2015 :14Available from: http://dx.doi.org/10.5051/jpis.2015.45.1.1410.5051/jpis.2015.45.1.1425722922 [Google Scholar] [CrossRef] [PubMed]
[71]. Türer ÇC, Ballı U, Güven B, Fetuin-A, serum amyloid A and tumor necrosis factor alpha levels in periodontal health and diseaseOral Dis 2017 23(3):379-86.10.1111/odi.1262527998014 [Google Scholar] [CrossRef] [PubMed]
[72]. Vuletic S, Taylor BA, Tofler GH, Chait A, Marcovina SM, Schenck K, SAA and PLTP activity in plasma of periodontal patients before and after full-mouth tooth extractionOral Dis 2008 14(6):514-19.10.1111/j.1601-0825.2007.01411.x18826383 [Google Scholar] [CrossRef] [PubMed]
[73]. Medina CMA, Garca JB, Zuluaga ICG, Association between serum amyloid A pathologic levels and periodontitisActa Med Colomb 2016 20(5):470-76. [Google Scholar]
[74]. Song LT, Lai W, Li JS, Mu YZ, Li CY, Jiang SY, The interaction between serum amyloid A and Toll-like receptor 2 pathway regulates inflammatory cytokine secretion in human gingival fibroblastsJ Periodontol 2020 91(1):129-37.10.1002/JPER.19-005031347700 [Google Scholar] [CrossRef] [PubMed]
[75]. Hirai K, Furusho H, Kawashima N, Xu S, de Beer MC, Battaglino R, Serum Amyloid A Contributes to Chronic Apical Periodontitis via TLR2 and TLR4J Dent Res 2019 98(1):117-25.10.1177/002203451879645630189157 [Google Scholar] [CrossRef] [PubMed]
[76]. Narayanan LL, Vaishnavi C, Endodontic microbiologyJ Conserv Dent 2010 13(4):233-39.10.4103/0972-0707.7338621217951 [Google Scholar] [CrossRef] [PubMed]
[77]. Siqueira JF Jr, Rôças IN, Bacterial pathogenesis and mediators in apical periodontitisBraz Dent J 2007 18(4):267-80.10.1590/S0103-6440200700040000118278296 [Google Scholar] [CrossRef] [PubMed]
[78]. Stashenko P, Teles R, D’Souza R, Periapical inflammatory responses and their modulation [Internet]Critical Reviews in Oral Biology & Medicine 1998 9:498-521.Available from: http://dx.doi.org/10.1177/1045441198009004070110.1177/104544119800900407019825224 [Google Scholar] [CrossRef] [PubMed]
[79]. Kawashima N, Stashenko P, Expression of bone-resorptive and regulatory cytokines in murine periapical inflammationArch Oral Biol 1999 44(1):55-66.10.1016/S0003-9969(98)00094-6 [Google Scholar] [CrossRef]
[80]. Sasaki H, Hirai K, Martins CM, Furusho H, Battaglino R, Hashimoto K, Interrelationship between periapical lesion and systemic metabolic disordersCurr Pharm Des 2016 22(15):2204-15.10.2174/138161282266616021614510726881444 [Google Scholar] [CrossRef] [PubMed]
[81]. Gordon S, Pattern recognition receptors: Doubling up for the innate immune responseCell 2002 111(7):927-30.10.1016/S0092-8674(02)01201-1 [Google Scholar] [CrossRef]
[82]. Janeway CA Jr, Medzhitov R, Innate immune recognitionAnnu Rev Immunol 2002 20:197-216.10.1146/annurev.immunol.20.083001.08435911861602 [Google Scholar] [CrossRef] [PubMed]
[83]. Akira S, Takeda K, Toll-like receptor signalling [Internet]. Vol. 4Nature Reviews Immunology 2004 :499-511.Available from: http://dx.doi.org/10.1038/nri139110.1038/nri139115229469 [Google Scholar] [CrossRef] [PubMed]
[84]. Harton JA, Linhoff MW, Zhang JY, Ting JP, Cutting Edge: CATERPILLER: A Large Family of Mammalian Genes Containing CARD, Pyrin, Nucleotide-Binding, and Leucine-Rich Repeat Domains [Internet]The Journal of Immunology 2002 169:4088-93.Available from: http://dx.doi.org/10.4049/jimmunol.169.8.408810.4049/jimmunol.169.8.408812370334 [Google Scholar] [CrossRef] [PubMed]
[85]. Bianchi ME, DAMPs, PAMPs and alarmins: All we need to know about danger [Internet]. Vol. 81Journal of Leukocyte Biology 2007 :1-5.Available from: http://dx.doi.org/10.1189/jlb.030616410.1189/jlb.030616417032697 [Google Scholar] [CrossRef] [PubMed]
[86]. Rubartelli A, Lotze MT, Inside, outside, upside down: Damage-associated molecular-pattern molecules (DAMPs) and redox [Internet]Trends in Immunology 2007 28:429-36.Available from: http://dx.doi.org/10.1016/j.it.2007.08.00410.1016/j.it.2007.08.00417845865 [Google Scholar] [CrossRef] [PubMed]
[87]. Vénéreau E, Ceriotti C, Bianchi ME, DAMPs from cell death to new lifeFront Immunol 2015 6:42210.3389/fimmu.2015.0042226347745 [Google Scholar] [CrossRef] [PubMed]
[88]. Schaefer L, Complexity of danger: The diverse nature of damage-associated molecular patternsJ Biol Chem 2014 289(51):35237-45.10.1074/jbc.R114.61930425391648 [Google Scholar] [CrossRef] [PubMed]
[89]. Zhang X, Mosser DM, Macrophage activation by endogenous danger signalsJ Pathol 2008 214(2):161-78.10.1002/path.228418161744 [Google Scholar] [CrossRef] [PubMed]
[90]. Smiley ST, King JA, Hancock WW, Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4J Immunol 2001 167(5):2887-94.10.4049/jimmunol.167.5.288711509636 [Google Scholar] [CrossRef] [PubMed]
[91]. Sokolove J, Zhao X, Chandra PE, Robinson WH, Immune complexes containing citrullinated fibrinogen costimulate macrophages via Toll-like receptor 4 and Fcγ receptorArthritis Rheum 2011 63(1):53-62.10.1002/art.3008120954191 [Google Scholar] [CrossRef] [PubMed]
[92]. Sohn DH, Sokolove J, Sharpe O, Erhart JC, Chandra PE, Lahey LJ, Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via Toll-like receptor 4Arthritis Res Ther 2012 14(1):R710.1186/ar355522225630 [Google Scholar] [CrossRef] [PubMed]