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1.  Acute-phase serum amyloid A production by rheumatoid arthritis synovial tissue 
Arthritis Research  2000;2(2):142-144.
Acute-phase serum amyloid A (A-SAA) is a major component of the acute-phase response. A sustained acute-phase response in rheumatoid arthritis (RA) is associated with increased joint damage. A-SAA mRNA expression was confirmed in all samples obtained from patients with RA, but not in normal synovium. A-SAA mRNA expression was also demonstrated in cultured RA synoviocytes. A-SAA protein was identified in the supernatants of primary synoviocyte cultures, and its expression colocalized with sites of macrophage accumulation and with some vascular endothelial cells. It is concluded that A-SAA is produced by inflamed RA synovial tissue. The known association between the acute-phase response and progressive joint damage may be the direct result of synovial A-SAA-induced effects on cartilage degradation.
Introduction:
Serum amyloid A (SAA) is the circulating precursor of amyloid A protein, the fibrillar component of amyloid deposits. In humans, four SAA genes have been described. Two genes (SAA1 and SAA2) encode A-SAA and are coordinately induced in response to inflammation. SAA1 and SAA2 are 95% homologous in both coding and noncoding regions. SAA3 is a pseudogene. SAA4 encodes constitutive SAA and is minimally inducible. A-SAA increases dramatically during acute inflammation and may reach levels that are 1000-fold greater than normal. A-SAA is mainly synthesized in the liver, but extrahepatic production has been demonstrated in many species, including humans. A-SAA mRNA is expressed in RA synoviocytes and in monocyte/macrophage cell lines such as THP-1 cells, in endothelial cells and in smooth muscle cells of atherosclerotic lesions. A-SAA has also been localized to a wide range of histologically normal tissues, including breast, stomach, intestine, pancreas, kidney, lung, tonsil, thyroid, pituitary, placenta, skin and brain.
Aims:
To identify the cell types that produce A-SAA mRNA and protein, and their location in RA synovium.
Materials and methods:
Rheumatoid synovial tissue was obtained from eight patients undergoing arthroscopic biopsy and at joint replacement surgery. Total RNA was analyzed by reverse transcription (RT) polymerase chain reaction (PCR) for A-SAA mRNA. PCR products generated were confirmed by Southern blot analysis using human A-SAA cDNA. Localization of A-SAA production was examined by immunohistochemistry using a rabbit antihuman A-SAA polyclonal antibody. PrimaryRA synoviocytes were cultured to examine endogenous A-SAA mRNA expression and protein production.
Results:
A-SAA mRNA expression was detected using RT-PCR in all eight synovial tissue samples studied. Figure 1 demonstrates RT-PCR products generated using synovial tissue from three representative RA patients. Analysis of RA synovial tissue revealed differences in A-SAA mRNA levels between individual RA patients.
In order to identify the cells that expressed A-SAA mRNA in RA synovial tissue, we analyzed primary human synoviocytes (n = 2). RT-PCR analysis revealed A-SAA mRNA expression in primary RA synoviocytes (n = 2; Fig. 2). The endogenous A-SAA mRNA levels detected in individual primary RA synoviocytes varied between patients. These findings are consistent with A-SAA expression in RA synovial tissue (Fig. 1). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) levels were relatively similar in the RA synoviocytes examined (Fig. 2). A-SAA protein in the supernatants of primary synoviocyte cultures from four RA patients was measured using ELISA. Mean values of a control and four RA samples were 77.85, 162.5, 249.8, 321.5 and 339.04 μg/l A-SAA, respectively, confirming the production of A-SAA protein by the primary RA synoviocytes. Immunohistochemical analysis was performed to localize sites of A-SAA production in RA synovial tissue. Positive staining was present in both the lining and sublining layers of all eight RA tissues examined (Fig. 3a). Staining was intense and most prominent in the cells closest to the surface of the synovial lining layer. Positively stained cells were evident in the perivascular areas of the sublining layer. In serial sections stained with anti-CD68 monoclonal antibody, positive staining of macrophages appeared to colocalize with A-SAA-positive cells (Fig. 3b). Immunohistochemical studies of cultured primary RA synoviocytes confirmed specific cytoplasmic A-SAA expression in these cells. The specificity of the staining was confirmed by the absence of staining found on serial sections and synoviocyte cells treated with IgG (Fig. 3c).
Discussion:
This study demonstrates that A-SAA mRNA is expressed in several cell populations infiltrating RA synovial tissue. A-SAA mRNA expression was observed in all eight unseparated RA tissue samples studied. A-SAA mRNA expression and protein production was demonstrated in primary cultures of purified RA synoviocytes. Using immunohistochemical techniques, A-SAA protein appeared to colocalize with both lining layer and sublining layer synoviocytes, macrophages and some endothelial cells. The detection of A-SAA protein in culture media supernatants harvested from unstimulated synoviocytes confirms endogenous A-SAA production, and is consistent with A-SAA mRNA expression and translation by the same cells. Moreover, the demonstration of A-SAA protein in RA synovial tissue, RA cultured synoviocytes, macrophages and endothelial cells is consistent with previous studies that demonstrated A-SAA production by a variety of human cell populations.
The RA synovial lining layer is composed of activated macrophages and fibroblast-like synoviocytes. The macrophage is the predominant cell type and it has been shown to accumulate preferentially in the surface of the lining layer and in the perivascular areas of the sublining layer. Nevertheless, our observations strongly suggest that A-SAA is produced not only by synoviocytes, but also by synovial tissue macrophage populations. Local A-SAA protein production by vascular endothelial cells was detected in some, but not all, of the tissues examined. The reason for the variability in vascular A-SAA staining is unknown, but may be due to differences in endothelial cell activation, events related to angiogenesis or the intensity of local inflammation.
The value of measuring serum A-SAA levels as a reliable surrogate marker of inflammation has been demonstrated for several diseases including RA, juvenile chronic arthritis, psoriatic arthropathy, ankylosing spondylitis, Behçet's disease, reactive arthritis and Crohn's disease. It has been suggested that serum A-SAA levels may represent the most sensitive measurement of the acute-phase reaction. In RA, A-SAA levels provide the strongest correlations with clinical measurements of disease activity, and changes in serum levels best reflect the clinical course.
A number of biologic activities have been described for A-SAA, including several that are relevant to the understanding of inflammatory and tissue-degrading mechanisms in human arthritis. A-SAA induces migration, adhesion and tissue infiltration of circulating monocytes and polymorphonuclear leukocytes. In addition, human A-SAA can induce interleukin-1β, interleukin-1 receptor antagonist and soluble type II tumour necrosis factor receptor production by a monocyte cell line. Moreover, A-SAA can stimulate the production of cartilage-degrading proteases by both human and rabbit synoviocytes. The effects of A-SAA on protease production are interesting, because in RA a sustained acute-phase reaction has been strongly associated with progressive joint damage. The known association between the acute-phase response and progressive joint damage may be the direct result of synovial A-SAA-induced effects on cartilage degradation.
Conclusion:
In contrast to noninflamed synovium, A-SAA mRNA expression was identified in all RA tissues examined. A-SAA appeared to be produced by synovial tissue synoviocytes, macrophages and endothelial cells. The observation of A-SAA mRNA expression in cultured RA synoviocytes and human RA synovial tissue confirms and extends recently published findings that demonstrated A-SAA mRNA expression in stimulated RA synoviocytes, but not in unstimulated RA synoviocytes.
PMCID: PMC17807  PMID: 11062604
acute-phase response; rheumatoid arthritis; serum amyloid A; synovial tissue
2.  Acute-Phase Serum Amyloid A: An Inflammatory Adipokine and Potential Link between Obesity and Its Metabolic Complications 
PLoS Medicine  2006;3(6):e287.
Background
Obesity is associated with low-grade chronic inflammation, and serum markers of inflammation are independent risk factors for cardiovascular disease (CVD). However, the molecular and cellular mechanisms that link obesity to chronic inflammation and CVD are poorly understood.
Methods and Findings
Acute-phase serum amyloid A (A-SAA) mRNA levels, and A-SAA adipose secretion and serum levels were measured in obese and nonobese individuals, obese participants who underwent weight-loss, and persons treated with the insulin sensitizer rosiglitazone. Inflammation-eliciting activity of A-SAA was investigated in human adipose stromal vascular cells, coronary vascular endothelial cells and a murine monocyte cell line. We demonstrate that A-SAA was highly and selectively expressed in human adipocytes. Moreover, A-SAA mRNA levels and A-SAA secretion from adipose tissue were significantly correlated with body mass index ( r = 0.47; p = 0.028 and r = 0.80; p = 0.0002, respectively). Serum A-SAA levels decreased significantly after weight loss in obese participants ( p = 0.006), as well as in those treated with rosiglitazone ( p = 0.033). The magnitude of the improvement in insulin sensitivity after weight loss was significantly correlated with decreases in serum A-SAA ( r = −0.74; p = 0.034). SAA treatment of vascular endothelial cells and monocytes markedly increased the production of inflammatory cytokines, e.g., interleukin (IL)-6, IL-8, tumor necrosis factor alpha, and monocyte chemoattractant protein-1. In addition, SAA increased basal lipolysis in adipose tissue culture by 47%.
Conclusions
A-SAA is a proinflammatory and lipolytic adipokine in humans. The increased expression of A-SAA by adipocytes in obesity suggests that it may play a critical role in local and systemic inflammation and free fatty acid production and could be a direct link between obesity and its comorbidities, such as insulin resistance and atherosclerosis. Accordingly, improvements in systemic inflammation and insulin resistance with weight loss and rosiglitazone therapy may in part be mediated by decreases in adipocyte A-SAA production.
Editors' Summary
Background.
Obesity often alters an individual's overall metabolism, which in turn leads to complications like diabetes, high blood pressure, and an increased risk of cardiovascular disease (disease of the heart and blood vessels, such as stroke or heart attacks). Having established a strong link between inflammation and cardiovascular disease, scientists now think that obesity might cause persistent low-level inflammation, and that this is the reason for the cardiovascular problems seen in many obese people. By better understanding the links between obesity, inflammation, and cardiovascular disease, the hope is that scientists may be able to find medications that can be given to obese people to reduce their risk of heart attacks and strokes.
Why Was This Study Done?
Previous research had suggested that a substance in the blood called A-SAA, which is raised by inflammation, might be a “missing link” between inflammation and cardiovascular disease, since an individual's baseline level of A-SAA is associated with the risk for cardiovascular disease (in other words, the higher the A-SAA, the higher the risk of cardiovascular disease). In the new study, researchers wanted to know whether the reason that obese people have a higher risk of cardiovascular disease is because they have higher blood levels of A-SAA.
What Did the Researchers Do and Find?
They found that obese people had higher levels of A-SAA in their blood. A-SAA appears to be produced in fat cells (or adipocytes) and then released into the blood. Obese people have higher numbers of fat cells, which could by itself account for the higher blood levels of A-SAA, but the researchers also found that the average fat cell from an obese individual produces and secretes higher levels of A-SAA than fat cells from lean individuals. When the researchers studied people who underwent weight loss, they found that A-SAA levels fell in response to weight loss, and this was associated with improvements in their metabolism. They then studied obese individuals who received the diabetes drug rosiglitazone (which is known to reduce inflammation). They found that even though these individuals did not lose weight, their A-SAA levels dropped as their metabolism improved. Trying to get at the mechanisms by which A-SAA might cause inflammation and diabetes, the researchers found that exposure to A-SAA can stimulate the activation of proinflammation molecules in a number of different cells, including blood vessel cells. It can also stimulate cells to break down fat stores and release fats, which could lead to metabolic complications and ultimately contribute to diabetes.
What Do These Findings Mean?
Together with similar results from other studies, the findings here suggest that A-SAA could promote inflammation, and that elevated levels of A-SAA in obese individuals could contribute to the chronic low-level inflammatory state that puts them at higher risk for cardiovascular complications. The authors speculate that drugs that reduce the blood levels of A-SAA might be useful as treatments for obese patients (to lower their risk of heart attacks and strokes). However, as they acknowledge, additional studies are needed to establish that A-SAA is indeed a causal link between obesity and inflammation and whether it plays a major role before it could be considered a promising drug target.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030287.
• MedlinePlus pages on obesity and cardiovascular disease
• US Centers for Disease Control and Prevention pages on obesity and cardiovascular disease
• Wikipedia pages on obesity and cardiovascular disease (note: Wikipedia is a free Internet encyclopedia that anyone can edit)
Higher levels of Acute-phase serum amyloid A (A-SAA), a proinflammatory adipokine, in obese individuals may contribute to the chronic low-level inflammatory state that puts them at higher risk for cardiovascular complications.
doi:10.1371/journal.pmed.0030287
PMCID: PMC1472697  PMID: 16737350
3.  C-reactive protein, haptoglobin, serum amyloid A and pig major acute phase protein response in pigs simultaneously infected with H1N1 swine influenza virus and Pasteurella multocida 
Background
Swine influenza (SI) is an acute respiratory disease caused by swine influenza virus (SIV). Swine influenza is generally characterized by acute onset of fever and respiratory symptoms. The most frequent complications of influenza are secondary bacterial pneumonia. The objective of this work was to study the acute phase proteins (APP) responses after coinfection of piglets with H1N1 swine influenza virus (SwH1N1) and Pasteurella multocida (Pm) in order to identify whether the individual APP response correlate with disease severity and whether APP could be used as markers of the health status of coinfected pigs.
Results
In all coinfected pigs clinical sings, including fever, coughing and dyspnea, were seen. Viral shedding was observed from 2 to 7 dpi. The mean level of antibodies against Pm dermonecrotoxin in infected piglets increase significantly from 7 dpi. Anti-SwH1N1 antibodies in the serum were detected from 7 dpi. The concentration of C-reactive protein (CRP) increased significantly at 1 dpi as compared to control pigs, and remained significantly higher to 3 dpi. Level of serum amyloid A (SAA) was significantly higher from 2 to 3 dpi. Haptoglobin (Hp) was significantly elevated from 3 dpi to the end of study, while pig major acute phase protein (Pig-MAP) from 3 to 7 dpi. The concentrations of CRP, Hp and SAA significantly increased before specific antibodies were detected. Positive correlations were found between serum concentration of Hp and SAA and lung scores, and between clinical score and concentrations of Pig-MAP and SAA.
Conclusions
The results of current study confirmed that monitoring of APP may revealed ongoing infection, and in this way may be useful in selecting clinically healthy pigs (i.e. before integration into an uninfected herd). Present results corroborated our previous findings that SAA could be a potentially useful indicator in experimental infection studies (e.g. vaccine efficiency investigations) or as a marker for disease severity, because of correlation observed between its concentration in serum and disease severity (lung scores, clinical scores).
doi:10.1186/1746-6148-9-14
PMCID: PMC3554491  PMID: 23332090
Acute phase proteins; Experimental coinfection; Swine influenza; Pasteurella multocida
4.  Establishment of a Transgenic Mouse Model Specifically Expressing Human Serum Amyloid A in Adipose Tissue 
PLoS ONE  2011;6(5):e19609.
Obesity and obesity co-morbidities are associated with a low grade inflammation and elevated serum levels of acute phase proteins, including serum amyloid A (SAA). In the non-acute phase in humans, adipocytes are major producers of SAA but the function of adipocyte-derived SAA is unknown. To clarify the role of adipocyte-derived SAA, a transgenic mouse model expressing human SAA1 (hSAA) in adipocytes was established. hSAA expression was analysed using real-time PCR analysis. Male animals were challenged with a high fat (HF) diet. Plasma samples were subjected to fast protein liquid chromatography (FPLC) separation. hSAA, cholesterol and triglyceride content were measured in plasma and in FPLC fractions. Real-time PCR analysis confirmed an adipose tissue-specific hSAA gene expression. Moreover, the hSAA gene expression was not influenced by HF diet. However, hSAA plasma levels in HF fed animals (37.7±4.0 µg/mL, n = 7) were increased compared to those in normal chow fed animals (4.8±0.5 µg/mL, n = 10; p<0.001), and plasma levels in the two groups were in the same ranges as in obese and lean human subjects, respectively. In FPLC separated plasma samples, the concentration of hSAA peaked in high-density lipoprotein (HDL) containing fractions. In addition, cholesterol distribution over the different lipoprotein subfractions as assessed by FPLC analysis was similar within the two experimental groups. The established transgenic mouse model demonstrates that adipose tissue produced hSAA enters the circulation, resulting in elevated plasma levels of hSAA. This new model will enable further studies of metabolic effects of adipose tissue-derived SAA.
doi:10.1371/journal.pone.0019609
PMCID: PMC3097194  PMID: 21611116
5.  Murine model for human secondary amyloidosis: genetic variability of the acute-phase serum protein SAA response to endotoxins and casein 
The Journal of Experimental Medicine  1976;144(4):1121-1127.
The serum precursor SAA of the secondary amyloid protein AA has been detected by solid-phase radioimmunoassay as a normal serum alpha- globulin of mol wt 160,000, which dissociates to a more stable 12,500 dalton moiety on treatment with formic acid. In 12 strains of mice, including T-cell-deficient nude mice, treated with the amyloid-inducing agents lipopolysaccharide (LPS) or casein, SAA behaved as an acute- phase reactant. SAA concentration rose to about 750 mug/ml by 24 h and returned to less than 1 mug/ml by 48 h. Since the amyloid-resistant colchicine-treated mice and AJ mice had a normal SAA response to LPS, it appears that their resistance to amyloid induction is due to the nature of their SAA processing rather than decreased SAA production. C3H/HeJ mice, which have defective B-lymphocyte responses to LPS, required extremely high dosages of LPS to cause SAA elevation, although their SAA response to casein was normal. This suggests that SAA is an acute-phase protein produced as a result of B-lymphocyte stimulation. Preliminary evidence suggests that at the height of an acute SAA response, liver homogenates are particularly rich in protein AA cross- reacting material.
PMCID: PMC2190436  PMID: 978136
6.  Serum Amyloid A (SAA): a Novel Biomarker for Endometrial Cancer 
Cancer  2010;116(4):843-851.
Background
We investigated the expression of Serum-Amyloid-A (SAA) in endometrial endometrioid carcinoma (EEC), and evaluated its potential as a serum biomarker.
Methods
SAA gene and protein expression levels were evaluated in EEC and normal endometrial tissues (NEC), by real time-PCR, immunohistochemistry (IHC) and flow cytometry. SAA concentration in 194 serum samples from 50 healthy-women, 42 women with benign diseases and 102 patients including 49 grade-1, 38 grade-2 and 15 grade-3 EEC was also studied by a sensitive bead-based-immunoassay.
Results
SAA gene expression levels were significantly higher in EEC when compared to NEC (mean-copy-number by RT-PCR = 182 vs 1.9; P=0.001). IHC revealed diffuse cytoplasmic SAA protein staining in poorly differentiated EEC tissues. High intracellular levels of SAA were identified in primary EEC cell lines evaluated by flow cytometry and SAA was found to be actively secreted in vitro. SAA concentrations (μg/ml) had medians of 6.0 in normal healthy females and 6.0 in patients with benign disease (P=0.92). In contrast, SAA values in the serum of EEC patients had a median of 23.7 significantly higher than those of the healthy group (P=0.001) and benign group (P=0.001). Patients harboring G3 EEC were found to have SAA concentrations significantly higher than G1/G2 patients.
Conclusions
SAA is not only a liver-secreted-protein but is also an EEC-cell product. SAA is expressed and actively secreted by G3-EEC and it is present in high concentration in the serum of EEC patients. SAA may represent a novel biomarker for EEC to monitor disease recurrence and response to therapy.
doi:10.1002/cncr.24838
PMCID: PMC2819580  PMID: 20041483
Endometrial carcinoma; Serum Amyloid A; Biomarkers; Tumor markers
7.  Changes in Human Serum Amyloid A and C-Reactive Protein after Etiocholanolone-Induced Inflammation 
Journal of Clinical Investigation  1978;61(2):390-394.
Secondary amyloidosis is a complication of diseases characterized by recurrent acute inflammation. In this study, a standardized stimulus which induced fever and inflammation was given to six normal subjects (19-24 yr old) to follow the fluctuation in concentration of serum amyloid A (SAA), the precursor of the secondary amyloid fibril protein. After a single intramuscular injection of etiocholanolone (0.3 mg/kg), blood samples were drawn twice a day for 12 days for determination of SAA by solid phase radioimmunoassay. From a base line of <100 μg/ml, the SAA concentration began rising within 12 h to a maximum value at about 48 h of 1,350-1,800 μg/ml in three males and 380-900 μg/ml in three females and returned to base line by 4-5 days. The SAA response showed a similar time response to C-reactive protein (CRP), a well-documented acute phase protein which was assayed semiquantitatively by capillary tube precipitin reaction. CRP, but not SAA, showed a quantitative correlation with the amount of fever induced by etiocholanolone. One subject exhibited a second rise in SAA and CRP concentrations after acute over-indulgence with alcohol, suggesting that acute liver damage may have caused an acute phase reaction. Thus, a controlled episode of fever and inflammation produced a prompt and prolonged elevation of SAA and CRP concentrations. Unlike SAA, CRP has not been implicated in the pathogenesis of amyloidosis, although its relationship to the P component of amyloid has recently been established.
PMCID: PMC372549  PMID: 621279
8.  Amyloid A gene family expression in different mouse tissues 
The Journal of Experimental Medicine  1986;164(6):2006-2017.
Serum amyloid A (SAA) is a major acute-phase reactant and apoprotein of high density lipoprotein (HDL). SAA is encoded by a family of three active genes. We examined hepatic expression and searched for extrahepatic expression of the three SAA mRNAs after injection with casein or LPS. Studies using an SAA cDNA, which detects all three SAA mRNAs, revealed that after casein injection liver SAA mRNA was elevated approximately 1,000-fold. Adrenal gland expressed SAA mRNA at a low level (0.5% of hepatic level), and was the only extrahepatic tissue with elevated SAA mRNA after casein injection. The small intestine, primarily the ileum, and the large intestine of unstimulated control animals contained 5- and 15-fold higher SAA mRNA levels than control liver. LPS also elevated liver SAA mRNA approximately 1,000-fold. However, in contrast to casein injection, every extrahepatic tissue examined expressed SAA mRNA. Lung and kidney contained 2-5% and large intestine contained nearly 10% of SAA mRNA levels found in liver RNA. SAA mRNA levels were lower in the remaining tissues and ranged from 0.1% in the brain and pancreas to 1.0% in the small intestine, with the ileum containing 50-fold more than the duodenum. Analysis of liver with SAA1, SAA2, and SAA3 mRNA-specific oligonucleotide probes revealed that SAA1 and SAA2 mRNA were elevated approximately 50-fold higher than SAA3 mRNA after casein administration. LPS, however, induced all three SAA mRNAs equally. In extrahepatic tissues, SAA1, SAA2, and SAA3 mRNAs were expressed differentially and can be grouped into three general classes: tissues expressing all three genes, tissues expressing SAA1 and SAA3, and tissues expressing predominantly or only SAA3.
PMCID: PMC2188489  PMID: 3783088
9.  Expression of serum amyloid A in uterine cervical cancer 
Diagnostic Pathology  2014;9:16.
Background
As an acute-phase protein, serum amyloid A (SAA) is expressed primarily in the liver. However, its expression in extrahepatic tissues, especially in tumor tissues, was also demonstrated recently. In our study, we investigated the expression of SAA in uterine cervical carcinomas, and our results suggested its potential as a serum biomarker.
Methods
Quantitative real-time polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the SAA gene and protein expression levels in the tissues and sera of patients with non-neoplastic lesions (NNLs), cervical intraepithelial neoplasia (CIN) and cervical carcinoma (CC).
Results
Compared with NNLs, the SAA gene (SAA1 and SAA4) expression levels were significantly higher in uterine CC (mean copy numbers: 138.7 vs. 5.01, P < 0.000; and 1.8 vs. 0.079, P = 0.001, respectively) by real-time PCR. IHC revealed cytoplasmic SAA protein staining in tissues from adenocarcinoma and squamous cell carcinoma of the cervix. The median serum concentrations (μg/ml) of SAA were 6.02 in patients with NNLs and 10.98 in patients with CIN (P = 0.31). In contrast, the median serum SAA concentration was 23.7 μg/ml in uterine CC patients, which was significantly higher than the SAA concentrations of the NNL group (P = 0.002) and the CIN group (P = 0.024).
Conclusions
Our data suggested that SAA might be a uterine CC cell product. High SAA concentrations in the serum of CC patients may have a role in monitoring disease occurrence and could have therapeutic applications.
Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1433263219102962.
doi:10.1186/1746-1596-9-16
PMCID: PMC3907664  PMID: 24447576
Uterine cervical carcinoma; Serum amyloid A; Tumor marker
10.  Serum amyloid A (SAA): a novel biomarker for uterine serous papillary cancer 
British Journal of Cancer  2009;101(2):335-341.
Background:
Uterine serous papillary carcinoma (USPC) is a biologically aggressive variant of endometrial cancer. We investigated the expression of Serum Amyloid A (SAA) and evaluated its potential as a serum biomarker in USPC patients.
Methods:
SAA gene and protein expression levels were evaluated in USPC and normal endometrial tissues (NEC) by real-time PCR, immunohistochemistry (IHC), flow cytometry and by a sensitive bead-based immunoassay. SAA concentration in 123 serum samples from 51 healthy women, 42 women with benign diseases, and 30 USPC patients were also studied.
Results:
SAA gene expression levels were significantly higher in USPC when compared with NEC (mean copy number by RT–PCR=162 vs 2.21; P=0.0002). IHC revealed diffuse cytoplasmic SAA protein staining in USPC tissues. High intracellular levels of SAA were identified in primary USPC cell lines evaluated by flow cytometry and SAA was found to be actively secreted in vitro. SAA concentrations (μg ml−1) had a median (95% CIs) of 6.0 (4.0–8.9) in normal healthy females and 6.0 (4.2–8.1) in patients with benign disease (P=0.92). In contrast, SAA values in the serum of USPC patients had a median (95% CI) of 15.6 (9.2–56.2), significantly higher than those in the healthy group (P=0.0005) and benign group (P=0.0006). Receiver operating characteristics (ROC) analysis of serum SAA to classify advanced- and early-stage USPC yielded an area under the ROC curve of 0.837 (P=0.0024).
Conclusion:
SAA is not only a liver-secreted protein but is also a USPC cell product. SAA may represent a novel biomarker for USPC to assist in staging patients preoperatively, and to monitor early-disease recurrence and response to therapy.
doi:10.1038/sj.bjc.6605129
PMCID: PMC2720219  PMID: 19536090
uterine serous papillary cancer; serum amyloid A; biomarkers; endometrial carcinoma; tumour markers
11.  Lack of acute phase response in the livers of mice exposed to diesel exhaust particles or carbon black by inhalation 
Background
Epidemiologic and animal studies have shown that particulate air pollution is associated with increased risk of lung and cardiovascular diseases. Although the exact mechanisms by which particles induce cardiovascular diseases are not known, studies suggest involvement of systemic acute phase responses, including C-reactive protein (CRP) and serum amyloid A (SAA) in humans. In this study we test the hypothesis that diesel exhaust particles (DEP) – or carbon black (CB)-induced lung inflammation initiates an acute phase response in the liver.
Results
Mice were exposed to filtered air, 20 mg/m3 DEP or CB by inhalation for 90 minutes/day for four consecutive days; we have previously shown that these mice exhibit pulmonary inflammation (Saber AT, Bornholdt J, Dybdahl M, Sharma AK, Loft S, Vogel U, Wallin H. Tumor necrosis factor is not required for particle-induced genotoxicity and pulmonary inflammation., Arch. Toxicol. 79 (2005) 177–182). As a positive control for the induction of an acute phase response, mice were exposed to 12.5 mg/kg of lipopolysaccharide (LPS) intraperitoneally. Quantitative real time RT-PCR was used to examine the hepatic mRNA expression of acute phase proteins, serum amyloid P (Sap) (the murine homologue of Crp) and Saa1 and Saa3. While significant increases in the hepatic expression of Sap, Saa1 and Saa3 were observed in response to LPS, their levels did not change in response to DEP or CB. In a comprehensive search for markers of an acute phase response, we analyzed liver tissue from these mice using high density DNA microarrays. Globally, 28 genes were found to be significantly differentially expressed in response to DEP or CB. The mRNA expression of three of the genes (serine (or cysteine) proteinase inhibitor, clade A, member 3C, apolipoprotein E and transmembrane emp24 domain containing 3) responded to both exposures. However, these changes were very subtle and were not confirmed by real time RT-PCR.
Conclusion
Our findings collectively suggest that Sap, Saa1 and Saa3 are not induced in livers of mice exposed to DEP or CB. Despite pulmonary inflammation in these mice, global transcriptional profiling of liver did not reveal any hepatic response following exposure by inhalation.
doi:10.1186/1743-8977-6-12
PMCID: PMC2673201  PMID: 19374780
12.  Acute phase reactants, challenge in the near future of animal production and veterinary medicine*  
The future of acute phase proteins (APPs) in science is discussed in this paper. Many functions and associated pathological processes of APPs are unknown. Extrahepatic formation in local tissues needs attention. Local serum amyloid A (SAA) formation may be involved in deposition of AA-amyloid induced by conformational change of SAA resulting in amyloid formation, having tremendous food safety implications. Amyloidogenesis is enhanced in mouse fed beta pleated sheet-rich proteins. The local amyloid in joints of chicken and mammary corpora amylacea is discussed. Differences in glycosylation of glycoproteins among the APPs, as has been shown for α1-acid glycoprotein, have to be considered. More knowledge on the reactivity patterns may lead to implication of APPs in the diagnostics and staging of a disease. Calculation of an index from values of several acute phase variables increases the power of APPs in monitoring unhealthy individuals in animal populations. Vaccinations, just as infections in eliciting acute phase response seem to limit the profitability of vaccines because acute phase reactions are contraproductive in view of muscle anabolism. Interest is focused on amino acid patterns and vitamins in view of dietary nutrition effect on sick and convalescing animals.
When inexpensive methodology such as liquid phase methods (nephelometry, turbidimetry) or protein array technology for rapid APP measurement is available, APPs have a future in routine diagnostics. Specific groups of patients may be screened or populations monitored by using APP.
doi:10.1631/jzus.2005.B0941
PMCID: PMC1390436  PMID: 16187407
Acute phase protein; Amino acid; Joint; Mammary gland; Mastitis; Serum amyloid A (SAA); Vitamin A
13.  Serum amyloid A is a chemoattractant: induction of migration, adhesion, and tissue infiltration of monocytes and polymorphonuclear leukocytes 
Serum amyloid A (SAA) is an acute phase protein that in the blood is bound to high density lipoproteins; SAA is secreted mainly by hepatocytes, and its concentration increases in the blood up to 1000 times during an inflammatory response. At present, its biological function is unclear. Since some forms of secondary amyloidosis are caused by deposition in tissues of peptides derived from the SAA and leukocytes seem to be involved in this process, we investigated the effect of human SAA on human monocytes and polymorphonuclear cells (PMN). When recombinant human SAA (rSAA) was used at concentrations corresponding to those found during the acute phase (> 0.8 microM), it induced directional migration of monocytes and polymorphonuclear leukocytes. Preincubation of rSAA with high density lipoproteins blocked this chemoattractant activity for both monocytes and PMN. rSAA also regulated the expression of the adhesion proteins CD11b and leukocyte cell adhesion molecule 1 and induced the adhesion of PMN and monocytes to umbilical cord vein endothelial cell monolayers. When subcutaneously injected into mice, rSAA recruited PMN and monocytes at the injection site. On the basis of these data, we suggest that SAA may participate in enhancing the migration of monocytes and PMN to inflamed tissues during an acute phase response.
PMCID: PMC2191543  PMID: 7516407
14.  Acute phase protein response in an experimental model of ovine caseous lymphadenitis 
Background
Caseous lymphadenitis (CLA) is a disease of small ruminants caused by Corynebacterium pseudotuberculosis. The pathogenesis of CLA is a slow process, and produces a chronic rather than an acute disease state. Acute phase proteins (APP) such as haptoglobin (Hp) serum amyloid A (SAA) and α1 acid glycoprotein (AGP) are produced by the liver and released into the circulation in response to pro-inflammatory cytokines. The concentration of Hp in serum increases in experimental CLA but it is not known if SAA and AGP respond in parallel or have differing response profiles.
Results
The concentration in serum of Hp, SAA and AGP in 6 sheep challenged with 2 × 105 cells of C. pseudotuberculosis showed significant increases (P < 0.05) compared to 3 unchallenged control sheep. By day 7 post infection. (p.i.) the Hp and SAA concentrations reached mean (± SEM) values of 1.65 ± 0.21 g/L and 18.1 ± 5.2 mg/L respectively. Thereafter, their concentrations fell with no significant difference to those of the control sheep by day 18 p.i.. In contrast, the serum AGP concentration in infected sheep continued to rise to a peak of 0.38 ± 0.05 g/L on day 13 p.i., after which a slow decline occurred, although the mean concentration remained significantly higher (P < 0.05) than the control group up to 29 days p.i.. Specific IgG to phospholidase D of C. pseudotuberculosis became detectable at 11 days p.i. and continued to rise throughout the experiment.
Conclusion
The serum concentrations of Hp, SAA and AGP were raised in sheep in an experimental model of CLA. An extended response was found for AGP which occurred at a point when the infection was likely to have been transforming from an acute to a chronic phase. The results suggest that AGP could have a role as a marker for chronic conditions in sheep.
doi:10.1186/1746-6148-3-35
PMCID: PMC2235841  PMID: 18093286
15.  Serum amyloid A protein in acute viral infections. 
Archives of Disease in Childhood  1993;68(2):210-214.
Concentrations of serum amyloid A protein (SAA) were measured in 254 children with viral diseases, including measles, varicella, rubella, mumps, echo-30 meningitis, chronic hepatitis B and C, and in eight with Kawasaki disease. Latex agglutination nephelometric immunoassay was used for assaying SAA. In 191 out of 195 patients (98%), SAA concentrations became markedly raised in the acute phase of the viral disease: measles (97%), varicella (100%), mumps (95%), and echo-30 meningitis (99%) with mean titres of 82.4, 80.5, 60.2, 75.2, and 101.1 micrograms/ml respectively. This increase in SAA was followed by a rapid return to normal concentrations (< 5 micrograms/ml) during convalescence. Remarkably higher concentrations of SAA (mean 1630 micrograms/ml) were detected in the acute phase of patients with Kawasaki disease, but in most of the children with chronic hepatitis B or C, the titres of SAA remained normal. There was no close correlation between SAA and serum concentrations for alpha 1-acid glycoprotein, beta 2-microglobulin, transferrin, and IgG. There was a clear correlation between SAA and C reactive protein concentrations, although SAA showed a greater incremental change than C reactive protein in the acute phase. In the acute phase of these viral diseases, 56% of the patients had raised SAA concentrations (> or = 5 micrograms/ml) with normal C reactive protein concentrations (< 5 micrograms/ml). These results indicate that SAA could be useful as an inflammatory marker in children with acute viral infections.
PMCID: PMC1029237  PMID: 8481043
16.  Serum amyloid A protein concentration in bone marrow transplantation for beta thalassaemia. 
Journal of Clinical Pathology  1992;45(4):348-351.
AIMS: To investigate whether serum amyloid A protein (SAA) and C-reactive protein (CRP) concentrations could be used in the management of beta thalassaemic patients undergoing bone marrow transplantation (BMT). METHODS: Serum SAA and CRP concentrations were determined in paired samples from 66 patients with beta thalassaemia before and after BMT. Serum SAA concentrations were determined by an enzyme linked immunoassay (EIA); serum CRP concentrations were determined by a nephelometric assay. RESULTS: Serum SAA concentrations before transplantation were significantly higher in the group that subsequently rejected the transplant than the group without complications. SAA concentrations increased after BMT in acute graft versus host disease (GvHD) and rejection. No significant increase in SAA or CRP was found in chronic GvHD. Increases in serum in SAA and CRP concentrations were not related to concomitant infection episodes. CONCLUSIONS: The different acute phase response in acute GvHD and rejection compared with chronic GvHD suggests that different immunopathogenic mechanisms are responsible.
PMCID: PMC495278  PMID: 1577974
17.  Colocalization of Serum Amyloid A with Microtubules in Human Coronary Artery Endothelial Cells 
Serum amyloid A (SAA) acts as a major acute phase protein and represents a sensitive and accurate marker of inflammation. Besides its hepatic origin, as the main source of serum SAA, this protein is also produced extrahepatically. The mRNA levels of SAA become significantly elevated following proinflammatory stimuli, as well as, are induced through their own positive feedback in human primary coronary artery endothelial cells. However, the intracellular functions of SAA are so far unknown. Colocalization of SAA with cytoskeletal filaments has previously been proposed, so we analyzed the colocalization of SAA with all three cytoskeletal elements: actin filaments, vimentin filaments, and microtubules. Immunofluorescent double-labeling analyses confirmed by PLA method revealed a strict colocalization of SAA with microtubules and a very infrequent attachment to vimentin while the distribution of actin filaments appeared clearly separated from SAA staining. Also, no significant colocalization was found between SAA and endomembranes labeled with the fluorescent lipid stain DiO6. However, SAA appears to be located also unbound in the cytosol, as well as inside the nucleus and within nanotubes extending from the cells or bridging neighboring cells. These different locations of SAA in endothelial cells strongly indicate multiple potential functions of this protein.
doi:10.1155/2011/528276
PMCID: PMC3205747  PMID: 22131810
18.  Acute Phase Proteins in Response to Dictyocaulus viviparus Infection in Calves 
Acta Veterinaria Scandinavica  2004;45(2):79-86.
Three experiments were carried out to examine the acute phase response, as measured by the acute phase proteins (APP) haptoglobin, serum amyloid A (SAA) and fibrinogen, in calves infected with lungworm, Dictyocaulus vivparus. In addition, eosinophil counts were analysed. Three different dose models were used in 3 separate experiments: I) 250 D. viviparus infective third stage larvae (L3) once daily for 2 consecutive days, II) 100 D. viviparus L3 once daily for 5 consecutive days, and III) 2000 L3 once. All 3 dose regimes induced elevated levels of haptoglobin, SAA and fibrinogen, although there was considerable variation both between and within experiments. A significant increase was observed in all 3 APP at one or several time points in experiment I and III, whereas in experiment II, the only significant elevation was observed for fibrinogen at one occasion. The eosinophil numbers were significantly elevated in all 3 experiments. The results show that lungworm infection can induce an acute phase response, which can be monitored by the selected APP. Elevated APP levels in combination with high numbers of eosinophils in an animal with respiratory disease may be used as an indicator of lung worm infection, and help the clinician to decide on treatment. However, high numbers of eosinophils and low levels of APP do not exclude a diagnosis of lungworm. Thus, lungworm infection may not be detected if measurements of APP are used to assess calf health in herds or individual animals.
doi:10.1186/1751-0147-45-79
PMCID: PMC1820983  PMID: 15535088
lungworm; Dictyocaulus viviparus; acute phase proteins; calves; respiratory disease; haptoglobin; serum amyloid A; fibrinogen
19.  Optimal combinations of acute phase proteins for detecting infectious disease in pigs 
Veterinary Research  2011;42(1):50.
The acute phase protein (APP) response is an early systemic sign of disease, detected as substantial changes in APP serum concentrations and most disease states involving inflammatory reactions give rise to APP responses. To obtain a detailed picture of the general utility of porcine APPs to detect any disease with an inflammatory component seven porcine APPs were analysed in serum sampled at regular intervals in six different experimental challenge groups of pigs, including three bacterial (Actinobacillus pleuropneumoniae, Streptococcus suis, Mycoplasma hyosynoviae), one parasitic (Toxoplasma gondii) and one viral (porcine respiratory and reproductive syndrome virus) infection and one aseptic inflammation. Immunochemical analyses of seven APPs, four positive (C-reactive protein (CRP), haptoglobin (Hp), pig major acute phase protein (pigMAP) and serum amyloid A (SAA)) and three negative (albumin, transthyretin, and apolipoprotein A1 (apoA1)) were performed in the more than 400 serum samples constituting the serum panel. This was followed by advanced statistical treatment of the data using a multi-step procedure which included defining cut-off values and calculating detection probabilities for single APPs and for APP combinations. Combinations of APPs allowed the detection of disease more sensitively than any individual APP and the best three-protein combinations were CRP, apoA1, pigMAP and CRP, apoA1, Hp, respectively, closely followed by the two-protein combinations CRP, pigMAP and apoA1, pigMAP, respectively. For the practical use of such combinations, methodology is described for establishing individual APP threshold values, above which, for any APP in the combination, ongoing infection/inflammation is indicated.
doi:10.1186/1297-9716-42-50
PMCID: PMC3072945  PMID: 21414190
20.  A Murine Model of Obesity with Accelerated Atherosclerosis 
Obesity (Silver Spring, Md.)  2009;18(1):35-41.
The epidemic of obesity sweeping developed nations is accompanied by an increase in atherosclerotic cardiovascular diseases. Dyslipidemia, diabetes, hypertension and obesity are risk factors for cardiovascular disease. However, delineating the mechanism of obesity-accelerated atherosclerosis has been hampered by a paucity of animal models. Similar to humans, apolipoprotein E deficient (apoE−/−) mice spontaneously develop atherosclerosis over their lifetime. To determine if apoE−/− mice would develop obesity with accelerated atherosclerosis, we fed mice diets containing 10 (LF) or 60 (HF) kcal % from fat for 17 weeks. Mice fed the HF diet had a marked increase in body weight and atherosclerotic lesion formation compared to mice fed the LF diet. There were no significant differences between groups in serum total cholesterol, triglycerides, or leptin concentrations. Plasma concentrations of the acute phase reactant serum amyloid A (SAA) are elevated in both obesity and cardiovascular disease. Accordingly, plasma SAA concentrations were increased 4.0 fold (P < 0.01) in mice fed the HF diet. SAA was associated with both pro- and anti-atherogenic lipoproteins in mice fed the HF diet compared to those fed the LF diet, in which SAA was primarily associated with the anti-atherogenic lipoprotein high density lipoprotein (HDL). Moreover, SAA was localized with apolipoprotein (apo)B-containing lipoproteins and biglycan in the vascular wall. Taken together, these data suggest male apoE deficient mice are a model of metabolic syndrome and that chronic low level inflammation associated with increased SAA concentrations may mediate atherosclerotic lesion formation.
doi:10.1038/oby.2009.176
PMCID: PMC2811527  PMID: 19498343
21.  Expression of Shelterin Component POT1 Is Associated with Decreased Telomere Length and Immunity Condition in Humans with Severe Aplastic Anemia 
Journal of Immunology Research  2014;2014:439530.
Abnormal telomere attrition has been found to be closely related to patients with SAA in recent years. To identify the incidence of telomere attrition in SAA patients and investigate the relationship of telomere length with clinical parameters, SAA patients (n = 27) and healthy controls (n = 15) were enrolled in this study. Telomere length of PWBCs was significantly shorter in SAA patients than in controls. Analysis of gene expression of Shelterin complex revealed markedly low levels of POT1 expression in SAA groups relative to controls. No differences in the gene expression of the other Shelterin components—TRF1, TRF2, TIN2, TPP1, and RAP1—were identified. Addition of IFN-γ to culture media induced a similar fall in POT1 expression in bone marrow cells to that observed in cells cultured in the presence of SAA serum, suggesting IFN-γ is the agent responsible for this effect of SAA serum. Furthermore, ATR, phosphorylated ATR, and phosphorylated ATM/ATR substrate were all found similarly increased in bone marrow cells exposed to SAA serum, TNF-α, or IFN-γ. In summary, SAA patients have short telomeres and decreased POT1 expression. TNF-α and IFN-γ are found at high concentrations in SAA patients and may be the effectors that trigger apoptosis through POT1 and ATR.
doi:10.1155/2014/439530
PMCID: PMC4033360  PMID: 24892036
22.  mRNA expression and release of interleukin-8 induced by serum amyloid A in neutrophils and monocytes. 
Mediators of Inflammation  2003;12(3):173-178.
The acute phase response is a systemic reaction to inflammatory processes characterized by multiple physiological adaptations, including the hepatic synthesis of acute-phase proteins. In humans, serum amyloid A (SAA) is one of the most prominent of these proteins. Despite the huge increase of serum levels of SAA in inflammation, its biological role remains to be elucidated, even though SAA is undoubtedly active in neutrophils. In a previous study, we reported that SAA induces the release of tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-8 from human blood neutrophils. Here, we extend our earlier study, focusing on the effect of SAA on neutrophil IL-8 transcription and on the signaling pathways involved. We demonstrate herein that SAA, in relatively low concentrations (0.4-100 microg/ml) compared with those found in plasma in inflammatory conditions, induces a dose-dependent release of IL-8 from neutrophils. The p38 mitogen-activated protein kinase inhibitor SB 203580 inhibits the IL-8 mRNA expression and the release of protein from neutrophils. The release of IL-8 from SAA-stimulated neutrophils is strongly suppressed by the addition of N-acetyl-l-cysteine, alpha-mercaptoethanol, glutathione, and dexamethasone. SAA also induces IL-8 expression and release from monocytes. In conclusion, SAA appears to be an important mediator of the inflammatory process, possibly contributing to the pool of IL-8 produced in chronic diseases, which may play a role in degenerative diseases.
doi:10.1080/0962935031000134897
PMCID: PMC1781605  PMID: 12857601
23.  A Seven-transmembrane, G Protein–coupled Receptor, FPRL1, Mediates the Chemotactic Activity of Serum Amyloid A for Human Phagocytic Cells  
We have previously reported (Badolato, R., J.M. Wang, W.J. Murphy, A.R. Lloyd, D.F. Michiel, L.L. Bausserman, D.J. Kelvin, and J.J. Oppenheim. 1994. J. Exp. Med. 180:203; Xu, L., R. Badolato, W.J. Murphy, D.L. Longo, M. Anver, S. Hale, J.J. Oppenheim, and J.M. Wang. 1995. J. Immunol. 155:1184.) that the acute phase protein serum amyloid A (SAA) is a potent chemoattractant for human leukocytes in vitro and mouse phagocytes in vivo. To identify the signaling mechanisms, we evaluated patterns of cross-desensitization between SAA and other leukocyte chemoattrctants. We found that the chemotactic bacterial peptide, N-formyl- methionyl-leucyl-phenylalanine (fMLP), was able to specifically attenuate Ca2+ mobilization in human phagocytes induced by SAA, but only at very high concentrations, suggesting that SAA uses a low affinity fMLP receptor. Here we demonstrate that SAA selectively induced Ca2+ mobilization and migration of HEK cells expressing FPRL1, a human seven-transmembrane domain phagocyte receptor with low affinity for fMLP, and high affinity for lipoxin A4. Furthermore, radiolabeled SAA specifically bound to human phagocytes and FPRL1-transfected 293 cells. In contrast, SAA was not a ligand or agonist for FPR, the high affinity fMLP receptor. Thus, SAA is the first chemotactic ligand identified for FPRL1. Our results suggest that FPRL1 mediates phagocyte migration in response to SAA.
PMCID: PMC2192984  PMID: 9892621
serum amyloid A; FPRL1; chemotaxis; calcium flux; receptor
24.  Field experience with two different vaccination strategies aiming to control infections with Actinobacillus pleuropneumoniae in a fattening pig herd 
Background
The prevalence of pleurisies recorded at slaughter is increasing in Sweden, and acute outbreaks of actinobacillosis that require antimicrobial treatments have become more frequent. As an increased use of antimicrobials may result in the development of antimicrobial resistance it is essential to develop alternative measures to control the disease. Vaccinations present an appealing alternative to antimicrobial treatments. The aim of this work was to evaluate the potential of two different vaccination strategies in a specialized fattening herd affected by actinobacillosis.
Methods
The study was conducted in a specialized fattening herd employing age segregated rearing in eight units. The herd suffered from infections caused by Actinobacillus pleuropneumoniae serotype 2, confirmed by necropsy and serology. The study included 54 batches of pigs grouped into five periods. Batches of pigs of the second period were vaccinated against actinobacillosis twice, and pigs in the fourth period were vaccinated three times. Batches of pigs of the first, third and fifth period were not vaccinated. Concentrations of serum antibodies to A. pleuropneumoniae and serum amyloid A (SAA) were analysed and production data were recorded.
Results
Despite vaccinating, medical treatments were required to reduce the impact of the disease. The mean incidence of individual treatments for respiratory diseases during the rearing period ranged from 0 to 4.7 ± 1.8%, and was greatest during the triple vaccination period (period IV; p < 0.05 when compared to other groups). A large proportion of the vaccinated pigs seroconverted to A. pleuropneumoniae serotype 2 in the absence of a SAA-response. The prevalence of pleuritis decreased from 25.4 ± 6.5% in the first period to 5.0 ± 3.7% in the fifth period (p < 0.001).
Conclusions
The vaccine did not effectively prevent clinical expression of A. pleuropneumoniae infections, but seroconversion to A. pleuropneumoniae in the absence of a SAA-response in a large number pigs indicated that the vaccine had activated the immune system. Further, the prevalence of pleuritis decreased with time. This indicates that vaccinations together with intensified medical treatments of affected pigs could be useful in reducing the impact of A. pleuropneumoniae serotype 2 infections.
doi:10.1186/1751-0147-52-23
PMCID: PMC2853545  PMID: 20334700
25.  Relative serum amyloid A (SAA) values: the influence of SAA1 genotypes and corticosteroid treatment in Japanese patients with rheumatoid arthritis 
Annals of the Rheumatic Diseases  2001;60(2):124-127.
OBJECTIVES—(1) To determine whether serum concentration of serum amyloid A (SAA) protein is influenced by the SAA1 allele in Japanese patients with rheumatoid arthritis (RA) as previously shown in a healthy control group; and (2) to analyse what factors, based on such an allelic bias, influence the relative SAA values of those patients.
METHODS—SAA and C reactive protein (CRP) concentrations together with SAA1 genotypes were determined in 316 Japanese patients with RA. The relative SAA values were evaluated as an SAA/CRP ratio.
RESULTS—Comparison of the three SAA1 homozygote groups showed that the SAA/CRP ratio was highest in the 1.5/1.5 group (mean 9.0, p<0.01 v the other two homozygote groups) followed by the 1.3/1.3 group (mean 7.2, NS v the 1.1/1.1 group) and the 1.1/1.1 group (mean 4.0). The SAA/CRP ratio was significantly higher in patients receiving corticosteroids regardless of the presence of allele 1.5. No clear differences in the ratio between patients with or without amyloidosis were found.
CONCLUSION—The SAA1.5 allele and corticosteroid treatment had a positive influence on SAA concentrations in serum. These findings are important when evaluating SAA concentration in inflammatory diseases and when considering the cause or treatment of amyloidosis.


doi:10.1136/ard.60.2.124
PMCID: PMC1753473  PMID: 11156544

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