Serum Serum Amyloid A Levels Research Articles

AB0069 Mechanism Elucidation of Effectiveness of IL-6 Blockade for Reduction of SAA Production and Amyloid A Deposition in AA Amyloidosis Patients with RA

BackgroundAA amyloidosis is a serious complication of chronic inflammatory and infectious diseases resulting from the deposition of amyloid A protein. Serum amyloid A (SAA), a precursor molecule of AA protein...

OP0116 Nitric Oxide and Endothelin-1 Levels in Familial Mediterranean Fever: Relationship with Inflammation and Amyloidosis

BackgroundFamilial Mediterranean Fever (FMF) is an autoinflammatory disease manifested by short febrile episodes of serositis. Severity of disease is linked to the occurrence of AA amyloidosis1 that involves many tissues,...

Serum amyloid-A in Behçet’s disease

Serum amyloid-A (SAA) is an acute phase protein, synthesized by the liver and previously investigated as a marker of disease activity in many rheumatologic disorders. Its significance in Behçet’s disease (BD), a chronic inflammatory disorder at the crossroad between autoimmune and autoinflammatory syndromes, is still unraveled. Our aim was to assess the role of SAA levels as a potential marker of disease activity in patients with BD. According to our findings, the occurrence of oral aphthosis, neurological impairment, and ocular disease is significantly associated with SAA serum levels higher than 30, 50, and 150 mg/L, respectively. We also suggest that increased SAA levels might identify a thrombotic risk in BD with previous or concurrent vascular involvement.

PW02-024-B - First report of AA amyloidosis in Blau syndrome

Systemic AA amyloidosis is a life-threatening complication of different chronic infectious and inflammatory diseases. The deposition of amyloid fibrils derived from the serum amyloid A (SAA) protein represents its pathological hallmark. A long lasting and increased serum level of SAA is a prerequisite to its development. The group of inherited autoinflammatory diseases includes different disorders consequence of a genetically-determined dysregulation of innate immune system. All these diseases are associated with a marked acute phase response. The incidence of AA amyloidosis varies widely among them, with the higher incidence in Muckle-Wells syndrome and in TNF receptor-associated periodic syndrome. Inversely, no cases of AA amyloidosis have been reported in some few inherited autoinflammatory diseases, including Blau syndrome, a dominantly-inherited disease caused by NOD2 mutations.

Serum amyloid A, phospholipase A2-IIA and C-reactive protein as inflammatory biomarkers for prostate diseases

Serum amyloid A (SAA), secreted group IIA phospholipase A₂ (sPLA₂-IIA), and C-reactive protein (CRP) are acute-phase proteins whose serum concentrations increase not only during inflammatory disorders, but also in the course of malignant diseases. In this study we analyzed serum levels of these inflammatory markers along with prostate-specific antigens (PSA) in patients with benign prostatic hyperplasia (BPH, n = 55), localized prostate cancers (PCa, n = 55), and metastatic prostate cancers (mPCa, n = 27) using immunological assays. We found that in comparison to healthy individuals (n = 55), patients with BPH, PCa and mPCa have elevated serum levels of SAA, sPLA₂-IIA, and CRP, in addition to elevated levels of PSA. Significant differences with respect to inflammatory biomarkers were found between localized and metastatic PCa (p < 0.001), suggesting a prognostic value of these parameters. In addition, serum concentrations of SAA and sPLA₂-IIA positively correlate with CRP in BPH patients (p < 0.05) and in patients with PCa and mPCa (p < 0.001), but not with PSA levels, Gleason score, or tumor stage, emphasizing a role of SAA and sPLA₂-IIA as circulating biomarkers of inflammation rather than of neoplastic transformation. In contrast to PSA, which differed significantly between BPH and localized PCa patients (p < 0.01), such a difference was not found for SAA, sPLA₂-IIA, and CRP. In order to elucidate whether the elevated levels of SAA and sPLA₂-IIA can be caused by cancer cell-associated synthesis, in vitro studies were performed. These analyses demonstrated the expression of SAA and sPLA₂-IIA in LNCaP and PC-3 prostate cell lines, which can be further upregulated by pro-inflammatory cytokines in a cell type-dependent manner. This might suggest that, in addition to the hepatic origin, SAA and sPLA₂-IIA can also be synthesized and secreted by prostatic cancer tissue itself. The results of the present study emphasize the utility of SAA, sPLA₂-IIA, and CRP as circulating biomarkers of inflammation during BPH development and PCa progression.

Preoperative level of serum amyloid A is superior to C-reactive protein in the prognosis of esophageal squamous cell carcinoma

Preoperative elevations in the levels of serum amyloid A (SAA) or C-reactive protein (CRP) have been reported to be prognostic indicators in several malignancies. The aim of this study is to evaluate the serum levels of SAA and CRP in the prognosis of esophageal squamous cell carcinoma (ESCC). In total, 252 patients with ESCC who had undergone surgery with curative-intent were retrospectively recruited. The specificity, sensitivity, and prognostic value of SAA or CRP levels were measured as the area under the receiver operating characteristic (ROC) curve (AUC). The clinical value of SAA and CRP levels as prognostic indicators was evaluated using Cox's proportional hazards model. The 1-, 3-, and 5-year overall survival (OS) rates for the entire cohort of patients with ESCC were 71.0%, 61.0%, and 43.0%, respectively. The correlation between the levels of SAA and CRP was significant (r(2) = 0. 685, P < 0.001). The ROC analysis showed that the levels of CRP were associated with a significantly lower overall accuracy than were the SAA levels (AUC, 0.615 vs. 0.880; P < 0.001). For the complete cohort, the median OS was 52.0 months longer in patients with low preoperative serum levels of SAA (72.0 months) compared with patients who had high SAA levels (20.0 months, P < 0.001). The median OS among patients with low CRP levels was also longer compared with the patients who had high CRP levels (72.0 vs. 51.0 months, respectively; P < 0.001). Subgroup analyses showed that the preoperative elevated levels of SAA could find significant differences in OS for stage I, stage II, and stage III (P < 0.001, P = 0.001, and P < 0.001, respectively), whereas the increased levels of CRP could only find a difference in OS for stage II cancers. After a multivariate analysis, preoperative elevated level of SAA was found to be an independently and significant prognostic factor (P < 0.001). Our study indicates that the preoperative levels of SAA and CRP can act as prognostic factors, and that elevated levels of these proteins are associated with negative effects on the survival of patients with ESCC. SAA showed a higher prognostic value than CRP in both cohort and subgroup analysis.

No Evidence for a Role of Adipose Tissue-Derived Serum Amyloid A in the Development of Insulin Resistance or Obesity-Related Inflammation in hSAA1+/− Transgenic Mice

Obesity is associated with a low-grade inflammation including moderately increased serum levels of the acute phase protein serum amyloid A (SAA). In obesity, SAA is mainly produced from adipose tissue and serum levels of SAA are associated with insulin resistance. SAA has been described as a chemoattractant for inflammatory cells and adipose tissue from obese individuals contains increased numbers of macrophages. However, whether adipose tissue-derived SAA can have a direct impact on macrophage infiltration in adipose tissue or the development of insulin resistance is unknown. The aim of this study was to investigate the effects of adipose tissue-derived SAA1 on the development of insulin resistance and obesity-related inflammation. We have previously established a transgenic mouse model expressing human SAA1 in the adipose tissue. For this report, hSAA1+/− transgenic mice and wild type mice were fed with a high fat diet or normal chow. Effects of hSAA1 on glucose metabolism were assessed using an oral glucose tolerance test. Real-time PCR was used to measure the mRNA levels of macrophage markers and genes related to insulin sensitivity in adipose tissue. Cytokines during inflammation were analyzed using a Proinflammatory 7-plex Assay. We found similar insulin and glucose levels in hSAA1 mice and wt controls during an oral glucose tolerance test and no decrease in mRNA levels of genes related to insulin sensitivity in adipose tissue in neither male nor female hSAA1 animals. Furthermore, serum levels of proinflammatory cytokines and mRNA levels of macrophage markers in adipose tissue were not increased in hSAA1 mice. Hence, in this model we find no evidence that adipose tissue-derived hSAA1 influences the development of insulin resistance or obesity-related inflammation.

Some acute phase reactants and cholesterol levels in serum of patient with Crimean-Congo haemorrhagic fever

The purpose of this study is to determine erythrocyte sedimentation rate (ESR), C - reactive protein (CRP), serum amyloid-A (SAA) and cholesterol levels in patients with Crimean-Congo Hemorrhagic Fever (CCHF) and determine the relationship of these parameters with the severity of disease. By polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) method 40 patients were diagnosed as CCHF and 39 volunteer without any systemic disease whose blood were taken and their serum separated. SAA, CRP and ESR were measured with ELISA, nephelometry and Mix-Rate x100 vital diagnostic device, respectively, in serum samples. High density lipoprotein (HDL), low density lipoprotein (LDL) and total cholesterol levels were determined by using autoanalyzer HDL, LDL and total cholesterol kit (Syncron LX20). Statistically significant difference was determined between patients and controls in terms of the levels of SAA, CRP, HDL, LDL and total cholesterol (p<0.05). However, there was no significant difference between the groups in terms of the levels of ESR. In addition, neither SAA, CRP, ESR nor HDL, LDL and total cholesterol levels varied with the severity of disease in the cases assessed (p>0.05). Using of CRP and SAA together might increase the sensitivity of diagnosis of CCHF infection. However, none of the parameters investigated in this study were found to be a proper marker of the prognosis in CCHF. Cholesterol levels were significantly decreased in patients with CCHF, which was suggested to be associated with the increased serum levels of SAA in the patient group.

Effects of subcutaneous and intravenous golimumab on inflammatory biomarkers in patients with rheumatoid arthritis: results of a phase 1, randomized, open-label trial

To evaluate the effects of the anti-TNF-α monoclonal antibody golimumab, administered by s.c. injection or i.v. infusion, on markers of inflammation in patients with RA. In this phase 1, open-label study, patients with active RA were randomized to receive s.c. golimumab 100 mg at baseline and every 4 weeks through week 20 (n = 33; group 1) or i.v. golimumab 2 mg/kg at baseline and week 12 (n = 16; group 2). Serum levels of CRP, IL-6, serum amyloid A (SAA), TNF receptor II (TNFRII), MMP-3, hyaluronic acid, haptoglobin, ferritin and haemoglobin and serum/urine hepcidin were measured at various time points. Associations between the biomarkers were assessed with Spearman's correlations. In both groups 1 and 2, decreases in mean serum levels of CRP, IL-6, SAA, TNFRII, MMP-3, haptoglobin, ferritin and hepcidin, and mean urine levels of hepcidin occurred within 1 week and were sustained through week 8. Decreases in concentrations of serum CRP, IL-6, SAA, MMP-3, hepcidin, ferritin and haptoglobin and urine hepcidin were maintained through week 24 in group 1, but began to reverse after week 8 in group 2. Among all patients, decreases in serum hepcidin correlated significantly with decreases in serum CRP and ferritin. Decreases in serum and urine concentrations of markers of inflammation occurred as early as 24 h after treatment with golimumab, and most of these improvements were sustained through week 24 in group 1.

Preliminary characterizations of a serum biomarker for sarcoidosis by comparative proteomic approach with tandem-mass spectrometry in ethnic Han Chinese patients

BackgroundThe diagnosis of sarcoidosis is still a significant challenge in China because of the need to exclude other diseases including granulomatous infections and malignancies that may be clinically and radiographically similar. The specific aim of the study is to search for serum protein biomarkers of sarcoidosis and to validate their clinical usefulness in differential diagnosis.MethodsSerum samples were collected from patients with sarcoidosis (n = 37), and compared to those from patients with tuberculosis (n = 20), other pulmonary diseases (n = 20), and healthy volunteers (n = 20) for determination of sarcoidosis-specific or -associated protein expression profiles. The first part of this study focused on proteomic analysis of serum from patients with sarcoidosis to identify a pattern of peptides capable of differentiating the studied populations using the ClinProt profiling technology based on mass spectrometry. Enzyme Linked Immunosorbent Assay (ELISA) was then used to verify corresponding elevation of the serum protein concentration of the potential biomarkers in the same patients sets. Receiver operating characteristic curve (ROC) analyses was performed to determine the optimal cutoff value for diagnosis. Immunohistochemistry was carried out to further confirm the protein expression patterns of the biomarkers in lung tissue.ResultsAn unique protein peak of M/Z 3,210 Daltons (Da) was found to be differentially expressed between the sarcoidosis and control groups and was identified as the N-terminal peptide of 29 amino acids (94-122) of serum amyloid A (SAA). ELISA confirmed that the serum SAA level was significantly higher in the sarcoidosis group than that of the other 3 control groups (p < 0.05). The cutoff for serum SAA concentration determined by ROC analysis was 101.98 ng/ml, with the sensitivity and specificity of 96.3% and 52.5%, respectively. Immunohistochemical staining showed that the SAA depositions in lung tissue of the sarcoidosis patients were also significantly more intense than in non-sarcoid lung tissue (p < 0.05).ConclusionThis is the first study to investigate serum protein markers in Chinese subjects with sarcoidosis. This study shows that the serum SAA expression profiles were different between the sarcoidosis and non-sarcoidosis groups. SAA may be a potential serum biomarker for ruling-out the diagnosis of sarcoidosis in Chinese subjects.

Two major ruminant acute phase proteins, haptoglobin and serum amyloid A, as serum biomarkers during active sheep scab infestation.

Two ruminant acute phase proteins (APPs), haptoglobin (Hp) and serum amyloid A (SAA), were evaluated as serum biomarkers (BMs) for sheep scab–a highly contagious ectoparasitic disease caused by the mite Psoroptes ovis, which is a major welfare and production threat worldwide. The levels of both APPs increased in serum following experimental infestation of sheep with P. ovis, becoming statistically significantly elevated from pre-infestation levels at 4 weeks post-infestation. Following successful treatment of infested sheep with an endectocide, Hp and SAA serum levels declined rapidly, with half lives of less than 3 days. In contrast, serum IgG levels which specifically bound the P. ovis-derived diagnostic antigen Pso o 2 had a half-life of 56 days. Taking into account pre-infestation serum levels, rapidity of response to infestation and test sensitivity at the estimated optimum cut-off values, SAA was the more discriminatory marker. These studies illustrated the potential of SAA and Hp to indicate current sheep scab infestation status and to augment the existing Pso o 2 serological assay to give disease-specific indications of both infestation and successful treatment.

Progression of non-small cell lung cancer: Diagnostic and prognostic utility of matrix metalloproteinase-2, C-reactive protein and serum amyloid A

Matrix metalloproteinase-2 (MMP-2) is known to degrade type IV collagen, which is a major component of the cellular basement membrane, and to be involved in the invasion and metastasis of cancer cells. On the other hand, C-reactive protein (CRP) and serum amyloid A (SAA) are acute inflammatory biomarkers that increase in various conditions including infection, inflammation, malignancy and tissue disturbance. In the present study, we examined the serum levels of MMP-2, CRP and SAA in patients with localized and metastatic non-small cell lung cancer (NSCLC) to establish the clinical significance and changes in these biomarkers during NSCLC progression. In this study, 24 NSCLC patients were diagnosed at the Kitasato University Hospital and compared with 13 healthy controls. Measurement of MMP-2 levels in serum was determined by measuring pro-MMP-2 using a one-step sandwich enzyme immunoassay. CRP and SAA levels in the serum were measured by latex nephelometry. The serum levels of MMP-2, CRP and SAA in metastatic NSCLC patients were significantly higher than in localized NSCLC patients (p<0.01). There was a significant positive correlation between serum MMP-2 and CRP levels as well as SAA levels in metastatic NSCLC patients (p<0.01). Therefore, quantitation of MMP-2, CRP and SAA in NSCLC patients may be an auxiliary indicator to monitor tumor progression and poor prognosis of NSCLC disease.

Laparoendoscopic Single-Site and Conventional Laparoscopic Radical Nephrectomy Result in Equivalent Surgical Trauma: Preliminary Results of a Single-Centre Retrospective Controlled Study

BackgroundLaparoendoscopic single-site surgery (LESS) has been developed in an attempt to further reduce the morbidity and scarring associated with surgical intervention, and it has been proposed to result in less induced surgical trauma than conventional laparoscopy. ObjectiveInvestigate the surgical trauma after LESS radical nephrectomy (LESS-RN) and laparoscopic radical nephrectomy (LRN). Design, setting, and participantsThis was a retrospective single-centre study including 66 patients: 31 patients underwent LESS-RN and 35 historical control patients who had undergone LRN. LRNs were performed between April 2008 and May 2009; LESS-RNs were performed between May 2009 and February 2011. InterventionLESS-RN and LRN were both performed via a transperitoneal access. Blood samples were collected pre- and intraoperatively at 6, 24, and 48h, and at 5 d postoperatively. MeasurementsSerum concentrations of acute-phase markers, C-reactive protein (CRP), serum amyloid A (SAA) antibody, and interleukin 6 (IL-6) and interleukin 10 (IL-10) were measured at each time point by enzyme-linked immunosorbent assay. Clinical data were collected by reviewing the patient’s records. Results and limitationsThere were no differences in serum CRP and SAA levels between the groups (CRP: p=0.12; SAA: p=0.09) at all time points. The changes in IL-6 levels in the LRN group were statistically significantly higher compared with the LESS-RN group at 6h after surgery (p=0.02), whereas the LESS-RN group showed statistically significantly higher IL-6 levels than the LRN group at 24h after surgery (p=0.02).Also, the serum levels of the anti-inflammatory cytokine IL-10 showed different kinetics in each group, being higher in the LESS-RN during the early postoperative phase (at 6h: p=0.01) and higher in the LRN group at 48h after surgery (p=0.01). The limitations of this study were its nonrandomized character and the small cohort of patients. ConclusionsLESS-RN is as effective as LRN without compromising surgical and postoperative outcomes, but it does not add any significant advantage in comparison with traditional LRN in terms of systemic stress response and surgical trauma.

Immune Functions of Serum Amyloid A

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

Clinicopathologic significance of expression of nuclear factor-κB RelA and its target gene products in gastric cancer patients

To assess the prognostic significance of nuclear factor-κB (NF-κB) and its target genes in gastric cancer. The tumor tissues of 115 patients with gastric cancer were immunohistochemically evaluated using monoclonal antibodies against NF-κB RelA. Preoperative serum levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) were assessed via enzyme-linked immuno-sorbent assay. C-reactive protein (CRP) and serum amyloid A (SAA) were measured via immunotrubidimetry. Positive rate of NF-κB RelA was 42.6%. NF-κB RelA expression in tumor tissues was also related to serum levels of IL-6 (P = 0.044) and CRP (P = 0.010). IL-6, SAA, CRP were related to depth of invasion, VEGF and SAA were correlated with lymph node metastasis. IL-6, VEGF, SAA and CRP were related to the stage. Univariate analysis demonstrated that immunostaining of NF-κB RelA, levels of IL-6, VEGF, SAA were significantly related with both disease free survival and overall survival (OS). Multivariate analysis verified that NF-κB RelA [hazard ratio (HR): 3.40, P = 0.024] and SAA (HR: 3.39, P = 0.045) were independently associated with OS. Increased expression of NF-κB RelA and high levels of serum SAA were associated with poor OS in gastric cancer patients.

Levels of acute inflammatory biomarkers in advanced prostate cancer patients with α2-macroglobulin deficiency

C-reactive protein (CRP), serum amyloid A (SAA), interleukin-6 (IL-6), α1-antitrypsin (α1AT), α1-acid glycoprotein (α1AG) and ceruloplasmin (CP) are acute inflammatory biomarkers that increase in various conditions including infection, inflammation, malignancy and tissue disturbance. In contrast, α2-macroglobulin (α2M) is involved in inflammation through its function as a carrier protein of IL-6. We had previously reported on advanced prostate cancer (PCa) patients with multiple distant bone metastases in whom serum α2M levels were markedly decreased (α2M deficiency). However, the relationship between serum levels of α2M and acute inflammatory biomarkers in PCa patients with or without α2M deficiency has not been demonstrated. In the present study, we examined serum levels of CRP, SAA, IL-6, α1AT, α1AG and CP in PCa patients with or without α2M deficiency to establish clinical significance and changes in these biomarkers during PCa disease progression. We found that upon addition of recombinant IL-6 (rIL-6) to serum from PCa patients with α2M deficiency, since a function of α2M is to bind and stabilize IL-6, the α2M-IL-6 complex and free endogenous IL-6 were not detectable. Serum levels of the α2M-independent markers, α1AT, α1AG and CP, in all PCa patients regardless of α2M deficiency were significantly higher than in healthy controls, but those of the α2M-dependent molecules, CRP, SAA and IL-6, were not increased in PCa patients with α2M deficiency. Therefore, quantitation of both α2M-dependent (CRP, SAA and IL-6) and α2M-independent (α1AT, α1AG and CP) acute inflammatory biomarkers in advanced PCa patients may be an auxiliary indicator, together with prostate-specific antigen (PSA), to monitor PCa disease progression.

Hydrochlorothiazide Compared to Candesartan Treatment Increases Adipose Tissue Gene Expression and Circulating Levels of Serum Amyloid A in Hypertensive Patients

Treatment of hypertension with angiotensin receptor blockers has been shown to reduce the risk of developing type 2 diabetes in comparison to thiazide diuretics and beta adrenergic blockers. Therefore, we wanted to study the effect of antihypertensive drugs on adipose tissue with respect to insulin resistance. In the MEDICA (MEchanisms for the DIabetes preventing effects of CAndesartan) study, 22 hypertensive, nondiabetic patients with abdominal obesity (10 men, 12 women) were randomized into 12-week treatment periods with candesartan, hydrochlorothiazide, and placebo according to a 3-way cross-over design. Subcutaneous adipose tissue biopsies were taken after 8 weeks treatment to analyze gene expression, glucose uptake capacity, insulin-signaling, and adipocyte size. Adipose tissue gene expression of serum amyloid A (SAA) was higher after hydrochlorothiazide treatment compared to candesartan (p=0.036), and this was in accordance with our previous finding on circulating SAA levels. Serum levels of E selectin were increased after hydrochlorothiazide compared to candesartan treatment (p=0.002) and lower after candesartan compared to placebo (p=0.002). In adipocytes, there were no significant differences between the treatments with respect to cell size, glucose uptake capacity, or insulin-signaling. In comparison to candesartan, hydrochlorothiazide raised the adipose tissue gene expression of SAA and the serum level of SAA as well as E selectin in hypertensive patients. Less adipose and systemic inflammation may be one explanation why candesartan is favorable in comparison to thiazide diuretics with respect to development of insulin resistance and type 2 diabetes.

Serum amyloid-A levels in neonatal necrotizing enterocolitis

We aimed to evaluate serum levels of serum amyloid-A (SAA) both in the diagnosis and monitoring the treatment response of necrotizing enterocolitis (NEC). Forty-five preterm neonates were enrolled in the study, including 15 infants with NEC, 15 with sepsis, and 15 healthy preterm infants. Pre- and posttreatment serum SAA levels were measured. Among patients with NEC, 11 had stage 1 and 4 had stage 2 disease according to the modified Bell's staging criteria. Baseline SAA levels of the infants with NEC were significantly higher than controls (P=0.013) and were significantly lower than those with sepsis (P=0.004). When infants with stage 1 and stage 2 NEC were analyzed separately, baseline SAA levels of the infants with stage 2 NEC were significantly higher than controls (P=0.027) than those with stage 1 NEC (P=0.018), but similar to those with sepsis. There was a trend that baseline SAA levels were also correlated with the Bell stage (r=0.501, P=0.057). Posttreatment SAA levels significantly decreased in infants with sepsis (P=0.002). Pre- and posttreatment SAA levels were similar in patients with stage 1 and 2 NEC. In conclusion, SAA rises in early stages of NEC and may aid in diagnosis as a serum marker.

Serum amyloid A level as a potential indicator of the status of endurance horses

Changes in serum levels of acute phase proteins (APPs) reflect the acute phase reaction, a rapid and nonspecific response to any tissue damage. Serum amyloid A (SAA) is the main APP in horses, which increases in various diseases, surgical injuries and after long distance endurance rides; however, this nonspecific parameter has not been investigated as an indicator of subclinical disorders, which may result in elimination during endurance competitions. To evaluate the serum concentration of SAA as a potential indicator for the status of horses prepared for long distance endurance rides (120 and 160 km). Twenty Arabian horses were tested and 12 were eliminated during the ride and 8 completed the distances. Routine haematological and biochemical tests and measurement of serum concentrations of SAA were carried out before and after the competition. Results were compared using the Mann Whitney U test. Before the competition all haematological and biochemical parameters varied within reference ranges with no differences between the eliminated horses and the ones that successfully finished the competition. After the rides creatine phosphokinase activity and neutrophil: lymphocyte ratio reflecting exercise-induced leukogram changes increased (P < 0.05) in both groups. Before the competition, the concentration of SAA remained within reference ranges; however, it was significantly (P < 0.05) lower in horses that successfully finished the competition than in eliminated ones (411.7 ± 144 ng/ml vs. 5809.5 ± 2242.7 ng/ml). After the ride SAA levels increased (P < 0.05) and were similar in both groups (13,833.8 ± 1354.3 ng/ml and 12,831.2 ± 1317.6 ng/ml). Serum SAA level was the only laboratory parameter that indicated most (66.6%) of the eliminated horses before entering the competition. None of the horses with SAA level higher than 1000 ng/ml completed the distance. Thus, it may be postulated that serum SAA concentration may indicate a poor status of a horse, resulting in elimination during a competition.

Expression of Serum Amyloid A in Human Ovarian Epithelial Tumors: Implication for a Role in Ovarian Tumorigenesis

Serum amyloid A (SAA) is an acute phase protein which is expressed primarily in the liver as a part of the systemic response to various injuries and inflammatory stimuli; its expression in ovarian tumors has not been described. Here, we investigated the expression of SAA in human benign and malignant ovarian epithelial tumors. Non-radioactive in situ hybridization applied on ovarian paraffin tissue sections revealed mostly negative SAA mRNA expression in normal surface epithelium. Expression was increased gradually as epithelial cells progressed through benign and borderline adenomas to primary and metastatic adenocarcinomas. Similar expression pattern of the SAA protein was observed by immunohistochemical staining. RT-PCR analysis confirmed the overexpression of the SAA1 and SAA4 genes in ovarian carcinomas compared with normal ovarian tissues. In addition, strong expression of SAA mRNA and protein was found in the ovarian carcinoma cell line OVCAR-3. Finally, patients with ovarian carcinoma had high SAA serum levels, which strongly correlated with high levels of CA-125 and C-reactive protein. Enhanced expression of SAA in ovarian carcinomas may play a role in ovarian tumorigenesis and may have therapeutic application.