Increase In Serum Amyloid A Research Articles

Optical coherence tomography assessment of disease activity in cryopyrin-associated periodic syndrome.

Cryopyrin-associated periodic syndrome is a rare autoinflammatory disease caused by gain-of-function mutations or variants in the NLRP3 gene. Clinically, patients suffer from a broad spectrum of both systemic and neurological symptoms. The aim of this study was to determine whether systemic inflammation demonstrated by serum amyloid A (SAA) elevation is associated with neuroinflammation assessed by optical coherence tomography (OCT). Thirty eyes of 15 patients with NLRP3 low penetrance mutations (PwNLRP3) and 20 eyes of 10 age- and sex-matched healthy controls were examined by spectral-domain OCT as part of routine clinical care. All retinal layers and clinical features were evaluated. At baseline no significant retinal neuroaxonal inflammation or degeneration was observed in all measured retinal layers amongst PwNLRP3 compared with healthy controls. In a pooled analysis of all individual OCT time points a significant difference regarding the macular retinal nerve fibre layer was detected. Increased levels of SAA showed a positive association with averaged combined outer plexiform layer and outer nuclear layer volumes (ρ < 0.0001, r2 = 0.35). In cryopyrin-associated periodic syndrome increased combined outer plexiform layer and outer nuclear layer volumes are mirrored by SAA increase, an acute phase reactant indicating systemic inflammation. Our findings identify OCT as a candidate biomarker to monitor subclinical neuroinflammation and to assess disease activity in PwNLRP3.

Serum amyloid A and risks of all-cause and cardiovascular mortality in chronic kidney disease: a systematic review and dose-response meta-analysis

Backgrounds The available literature on the correlation between serum amyloid A (SAA) and prognosis of chronic kidney disease (CKD) are limited, and the findings from existing studies are inconclusive. This meta-analysis aimed to evaluate the available evidence regarding the link between SAA and risks of all-cause and cardiovascular mortality in CKD patients. Additionally, we aimed to investigate the potential dose-response relationships, provided that adequate data is accessible. Methods Pubmed and Embase were searched for related literature (last update: 12 July 2023). The pooled effect estimates were calculated using random- or fixed-effects models depending on heterogeneity among studies. Results This meta-analysis incorporated 8 studies encompassing 2331 CKD patients. The findings revealed an 85% increase in all-cause mortality risk [hazard risk (HR) 1.85, 95% confidence interval (CI) 1.29–2.65] and a 39% increase in cardiovascular mortality risk (HR 1.07, 95% CI 1.07–1.80) when comparing the highest tertile of baseline SAA levels to the lowest tertile. Furthermore, a positive linear relationship between SAA and all-cause mortality risk was observed (P non-linearity = 0.959), with a 17.7% increase in risk for each 10 mg/L SAA increase (HR 1.177, 95% CI 1.055–1.313). Similarly, a linear relationship between SAA and cardiovascular mortality risk was identified (P non-linearity = 0.477) with a 19.3% increase in risk for each 10 mg/L SAA increase (HR 1.193, 95% CI 1.025–1.388). Conclusions This meta-analysis provided evidence that SAA levels are positively and linearly associated with risks of all-cause and cardiovascular mortality among CKD patients.

Serum amyloid A protein as a predictor of severity in coronavirus disease 2019-infected Egyptian patients

Background The coronavirus disease 2019 (COVID-19) pandemic is a worldwide pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus. Serum amyloid A (SAA) is an acute-phase protein secreted during the acute phase of inflammation and can be used to predict the severity of COVID-19 disease. When inflammatory stimuli occur, levels of SAA increase within hours and the magnitude of response becomes great and may be greater than that of C-reactive protein (CRP). Aim Assessment of the level of SAA in COVID-19 Egyptian patients to predict the severity of the disease. Patients and methods This was an observational case–control study conducted on 80 participants: 60 patients with RT-PCR positive and computed tomography chest for COVID-19 disease classified into three groups according to disease severity: group I (20 patients) mild cases, group II (20 patients) moderate cases, and group III (20 patients) severe cases, and 20 participants as a control group. All participants were investigated for complete blood count, Serum Glutamic Pyruvic Transaminase (SGPT), Serum Glutamic Oxaloacetic Transaminase (SGOT), blood urea, serum creatinine, CRP, D-dimer and SAA. Results There is no statistical significance among the comparison groups as regards SAA. There was a high statistically significant decrease in the number of lymphocytes in COVID-19 patient groups compared with the control group. There was a statistically significant difference as regards platelet count, CRP, D-dimer, serum urea, and creatinine among the groups (I, II, and III) compared with the control group. Conclusion Single use of SAA during the pandemic could not achieve prediction of severity or the prognosis of COVID-19.

Acupuncture Treatment Improves Transport Stress in Microminipigs Through the Acupoint in Ears.

This study aimed to investigate the effects of acupuncture treatment through the ear acupoints on transport stress in experimental microminipigs. Experiment 1: Six animals were equally divided into two groups (Control and Treatment). In the treatment group, before transportation (6 h; vehicle and plane), short, ultrathin circular transdermal needles were applied to locations corresponding to the acupoints on the apical area of both ears. Peripheral blood samples were collected from the cranial vena cava 2 days before and immediately after transportation. Blood stress markers, biochemistry indicators, and oxidative stress levels were examined. Experiment 2 (follow-up study: diarrhea incidence after transportation): Diarrhea incidence after transportation in the control and treatment groups was investigated. Experiment 1: Transport stress induced an increase in blood cortisol, serum amyloid A (SAA), glucose, non-esterified fatty acid, and derivatives of reactive oxygen metabolites (d-ROMs) and decreased the biological antioxidant potential (BAP)/d-ROMs ratio yet did not affect BAP. Acupuncture suppressed the increases in SAA and d-ROMs values and the decrease in BAP/d-ROMs ratio. Experiment 2: The total diarrhea incidence was 25% in the control group, whereas diarrhea was not observed in the treatment group. Acupuncture treatment suppresses hypothalamic-pituitary-adrenal function and, as a result, reduces transport stress without affecting the suppression of the central catecholaminergic system. Acupuncture treatment for transport stress can improve animal welfare.

Using systemic serum amyloid A as a biomarker for synovial structure infections in horses with acute limb wounds.

In postoperative monitoring of synovial structure infection due to limb wounds, early recognition of a recurrence of synovial infection is indispensable to prevent further damage to the affected synovial structure. This study evaluated the role of serum amyloid A (SAA) as a systemic biomarker in disease monitoring and correlated this tool with clinical variables. In this prospective cohort study, 55 horses with acute limb wounds were divided into two groups: those with (group 1, n=26) or without (group 2, n=29) a diagnosis of synovial structure penetration. SAA, lameness and body temperature were evaluated repeatedly and compared between groups. Correlations were explored between SAA and body temperature as well as lameness. The long-term outcome was also analysed. In both groups, SAA levels followed the characteristic rise-and-fall pattern observed in previous studies, with a significant increase up to a peak concentration within 48hours, followed by a constant decline. Lameness and body temperature did not change significantly. SAA was not found to correlate with clinical variables at all time points. Three horses in group 1 had a recurrence of synovial sepsis with an associated increase in SAA. The long-term outcome was good. A total of 71% of the study population returned to pre-injury performance levels. Repeated measurements of SAA accurately reflected the course of synovial inflammation and thus provided a reliable and rapidly available tool to monitor the disease course and to adapt the treatment regimen. SAA should be routinely added to the postoperative management of such cases.

Bronchial brush cytology, endobronchial biopsy, and SALSA immunohistochemistry in severe equine asthma.

Horses with severe equine asthma (SEA), also known as heaves and recurrent airway obstruction, have persistent neutrophilic inflammation of the lower airways. Cytologic evaluation of bronchoalveolar lavage (BAL) fluid is commonly used to confirm the clinical diagnosis of SEA. However, the utility of microscopic assessment of bronchial brushings, endobronchial biopsies, and immunohistochemical detection of disease-associated biomarkers for the diagnosis of SEA remain poorly characterized. Salivary scavenger and agglutinin (SALSA) has anti-inflammatory properties and downregulated gene expression in SEA; therefore, it was investigated as a tissue biomarker for airway and systemic inflammation. Six asthmatic and 6 non-asthmatic horses were exposed to an inhaled challenge. Before and after challenge, samples of BAL fluid, bronchial brushing, and endobronchial biopsy were collected. Location of SALSA in biopsies was determined, and immunohistochemical label intensity was computed using image analysis software. Serum amyloid A (SAA) was measured to assess systemic inflammation. After challenge, neutrophil proportions were significantly higher in asthmatic versus non-asthmatic horses in BAL fluid (least squares means, 95% confidence interval: 80.9%, 57.2% to 93.1%, vs 3.6%, 1.1% to 10.7%) and in brush cytology slides (39.5%, 7.7% to 83.6%, vs 0.2%, 0% to 2.3%), illustrating the potential of brush cytology as an alternate modality to BAL for assessing intraluminal inflammation. Bronchial histopathologic findings and intensity of SALSA immunolabeling in surface and glandular epithelium were similar in asthmatic and non-asthmatic horses, indicating limited changes in bronchial tissue from the inhaled challenge. Increases in SAA indicated systemic inflammation, but SALSA immunolabeling did not change significantly.

Correlation Between Serum Amyloid A and Antibody Response to West Nile Virus Vaccine Antigen in Healthy Horses

The purpose of this study was to establish if peak serum amyloid A (SAA) concentrations can be used to determine an appropriate immune response to a vaccine containing West Nile Virus (WNV) antigen. A pilot study with 20 clinically healthy horses was performed to identify peak SAA concentration postvaccination with a commercial multivalent WNV vaccine. Blood was collected for SAA at 0, 24, 48, 72, 96, 168 hours postvaccination. Serum for WNV serum neutralization antibody testing was obtained immediately prior to and 30 days postvaccination. An additional 40 horses underwent the study protocol, but with SAA measurements acquired at 0-hours and 72-hours postvaccination. Ninety percent of the population had an increase in SAA in response to WNV vaccination, though no significant correlation was identified between SAA peak and antibody titer fold changes. WNV antibody titer fold changes between pre- and post-vaccination revealed 57% of horses had increased fold changes, 30% had no fold changes and 13% had negative fold changes. There was a negative correlation between age and SAA response (P = .0008). The main conclusions were SAA response postvaccination against WNV does not appear to mirror antibody response. Age appears to significantly affect SAA response. Further, vaccination with WNV antigen may not consistently induce a positive increase in WNV antibodies.

Impact of radioiodine treatment on acute phase proteins in hyperthyroid cats.

ObjectivesThe aim of this study was to investigate the impact of radioiodine treatment (RIT) on the acute phase proteins (APPs) serum amyloid A (SAA), alpha-1-acid glycoprotein (AGP) and haptoglobin (Hp) in hyperthyroid cats.MethodsBetween June 2013 and November 2014, 33 hyperthyroid cats without clinical or laboratory signs of inflammatory or neoplastic disease and a body weight >2.5 kg were enrolled. Immediately before, and 12, 36, 72 h and 6 days after RIT, serum samples were obtained for determination of APP concentrations.ResultsBoth SAA and AGP concentrations changed significantly after RIT. The concentration of AGP increased gradually after treatment with a maximum concentration at the end of the study period (median baseline 398 μg/ml; median 6 days post-RIT 562 μg/ml [P = 0.001]). A relevant >two-fold increase in AGP was seen in 8/33 (24%) cats. SAA concentration increased significantly within 12 h (baseline 9.2 μg/ml; 12 h post-RIT 22.5 μg/ml [P = 0.012]). In 7/33 (21%) cats, a clinically relevant >10-fold increase in SAA was observed. Hp concentration showed no significant change (P = 0.12).Conclusions and relevanceRIT induced a mild, mainly not clinically relevant acute phase reaction (APR). AGP and SAA were useful APPs to determine RIT-induced APR.

Chronic Hemolysis, Oxidative Stress and Inflammation Contribute to Dysfunctional HDL in Sickle Cell Disease

IntroductionHypocholesterolemia was observed in sickle cell disease (SCD) patients according to various reports in the literature. It was previously linked to anemia and inflammation by others and to oxidative stress by our group. In this study we investigated the relationship between cholesterol metabolism, hemolysis, inflammation and oxidative stress in SCD.MethodsThe study consisted of pediatric SCD patients (N=34) and healthy controls (N=19). Patients were crisis-free and did not receive transfusion for the last 3 months.Hemolysis was assessed with the measurement of haptoglobin (Hpg), bilirubin and LDH. Hemin values were accepted as a representation of oxidative stress; while serum amyloid A (SAA) and myeloperoxidase (MPO) levels were measured to determine the level of inflammation.Hemin, SAA and MPO levels were measured by commercial kits while all other parameters including the lipid panel and liver function tests were measured by autoanalyzers in the clinical chemistry lab. Statistical analyses were performed with IBM SPSS v23.0. The study was approved by the Institutional Review Board of Mersin University.ResultsMean age of the patients and controls were 13.71±3.79 and 13.47±3.49 years respectively. Patient and control groups were similar in terms of age and sex. All values are given as patients vs. controls and mean±SD.Among the values representing hemolysis, statistically significant differences between groups were found for Hpg (3.84±16.18 mg/dL vs. 69.98±37.66 mg/dL, p<0.001), total and direct bilirubin (1.93±1.17 mg/dL vs. 0.27±0.14 mg/dL and 0.40±0.21 mg/dL vs. 0.06±0.04 mg/dL, p<0.001), and LDH (540.29±217.32 U/L vs. 202.79±49.46 U/L, p<0.001).Hemin levels, as an index of oxidative stress, were significantly higher in the patient group (9.52±8.75 mg/L vs. 0.27±0.01 mg/L, p<0.001).SAA and MPO levels which were accepted to determine the level of chronic inflammation were both significantly higher in the patient group (1.19±0.60 mg/L vs. 0.68±0.52 mg/L, p=0.013 and 76.53±31.03 μg/L vs. 44.56±8.29 μg/L, p=0.001; respectively).In the lipid panel, significant differences between groups were found in total cholesterol (116.97±17.22 mg/dL vs. 169.84±33.70 mg/dL, p<0.001), HDL (28.31±5.21 mg/dL vs. 50.95±12.95 mg/dL, p<0.001), LDL (70.80±11.96 mg/dL vs. 99.89±22.95 mg/dL, p<0.001), and apolipoprotein AI (149.61±54.88 mg/dL vs. 199.32±33.48 mg/dL, p=0.001); whereas no difference was found in apolipoprotein B (77.65±25.52 mg/dL vs. 81.57±13.96 mg/dL, p=0.541) levels.ConclusionPediatric SCD patients in this study had hypocholesterolemia reflected by low LDL and HDL levels. Apolipoprotein AI levels were also lower in patients suggesting either low production or increased catabolism of the HDL particle.The drastic decrease in Hpg levels and the increase in bilirubin and LDH values show the overwhelming chronic hemolysis in SCD. Hpg protects vascular endothelium by binding to hemoglobin. Hpg was also shown to protect Apo AI from oxidative damage. However, the consumption of Hpg in our patients may possibly render Apo AI open to the damaging effects of free radicals formed during hemolysis.Hemin is produced by the oxidation of free heme to the ferric state. Increased hemin levels in SCD patients, compared to the almost-undetectable levels in controls, may cause oxidative damage to plasma proteins and lipids as well as activating neutrophils with its oxidative effect. Apolipoproteins and lipids in the structure of HDL and LDL particles are targets for oxidative damage.The increase in SAA and MPO levels indicate the chronic inflammation in SCD. SAA is an important acute phase protein secreted by the liver during inflammation. It translocates Apo AI by incorporating into HDL and slows down reverse cholesterol transport by inhibiting cholesterol incorporation into HDL. A previous study reports SAA as a marker of crisis in SCD. Increased MPO release by the leukocytes was shown to oxidize Apo AI and disrupt its function in patients with cardiovascular disease. Therefore, increased MPO levels in our patients may contribute to the oxidative damage on the Apo AI of the HDL particle.Thus, the cumulative effect of chronic hemolysis, oxidative stress and inflammation in SCD may result with a pathological structural alteration in HDL and contribute to HDL dysfunction. The slowing down of reverse cholesterol transport may be an important cause of hypocholesterolemia in SCD. DisclosuresNo relevant conflicts of interest to declare.

Changes in the Secretion of Anti-Inflammatory Cytokines and Acute-Phase Proteins in the Uterus after Artificial Insemination in the Mare.

Simple SummarySemen deposition into the uterus during mating or artificial insemination induces a rapid inflammatory response, and, in susceptible mares, persistent endometritis can develop. Cytokines are mediators involved in the regulation of the inflammatory process, and acute phase proteins are the most sensitive indicators of the inflammatory process. Therefore, the aim of this research was to determine the secretion of anti-inflammatory cytokines and acute-phase proteins in the uterus before and after artificial insemination in the mare. The obtained results indicate that the status of the mare before artificial insemination has little effect on the response measured shortly after artificial insemination. The presence of intrauterine fluid during estrus is not connected with the inflammation parameters investigated in this study at 7 h post artificial insemination. Detailed examination of the mare’s reproductive tract before and after artificial insemination guarantees high fertility.The objective of the study was to evaluate the concentrations of interleukin-1 receptor antagonist (IL-1RA), interleukin-10 (IL-10), serum amyloid A (SAA) and haptoglobin (Hp) in uterine lavage fluid before and after artificial insemination (AI). Based on ultrasound examination, mares were divided into: Group 1 (n = 9), no fluid was detected in the uterus during estrus and 7 h after AI; Group 2 (n = 8), no fluid was detected in the uterus during estrus but 7 h after AI fluid was detected in the uterus; Group 3 (n = 8), fluid was detected in the uterus during estrus and also 7 h after AI. In all groups of mares, a significant increase in polymorphonuclear cells (PMN) and a significant increase in IL-1RA and SAA were recorded 7 h after AI. The obtained results show that, regardless of the status of the mare before AI, the endometrial response characterized by PMN influx, and SAA, Hp, IL-1RA and IL-10 production, is similar. The presence of intrauterine fluid during estrus is not connected with PMN influx but can impact uterine IL-1RA production at this time.

Acute-Phase Proteins of Healthy Horses and Horses Naturally Affected by Colic Syndrome

The purpose of this study was to evaluate and compare the serum proteinogram, identifying and quantifying the acute-phase proteins (APPs) of healthy horses and those naturally affected by colic syndrome. Blood samples were collected from 9 healthy horses and 17 horses with clinical (G1) or surgical (G2) colic at the time of arrival at the veterinary hospital (M0) and 24 (M1), 48 (M2), and 72 (M3) hours after the initiation of treatment. The APPs were separated by polyacrylamide gel electrophoresis (SDS-PAGE), and their concentrations were determined by computerized densitometry. Protein identification was performed using matrix assisted laser desorption/ionization-time of flight mass spectrometry. Nine APPs were identified: α2-macroglobulin, ceruloplasmin, transferrin, albumin, α1-antitrypsin, haptoglobin, α1-acid glycoprotein, apolipoprotein A1, and serum amyloid A. Ceruloplasmin (Cp) presented an elevation at M0 in G2 in relation to G1 and the control group (CG). Serum amyloid A (SAA) presented an elevation with a difference at M3 in G1 and G2, compared with CG. In the comparison between the time points within each group (G1 and G2), there was an increase in SAA in G2 with a difference at M1, M2, and M3. Cp and SAA were suitable for evaluating the acute-phase response in horses with colic. Cp was an indicator of colic with surgical resolution. SAA presented favorable behavior for its use as a biomarker to establish the prognosis in horses with colic. The serial measurement of these proteins was useful in differentiating the clinical or surgical treatment and prognosis of horses with this disorder.

Acute phase proteins and biomarkers of oxidative status in feline spontaneous malignant mammary tumours.

Acute phase proteins (APP) and biomarkers of oxidative status change in human and canine mammary tumours, however, they have not been studied in feline mammary tumours. The aims of this study were to investigate the APP and antioxidant responses in feline malignant mammary tumours, to evaluate their relation with tumour features, and to assess their prognostic value. Serum amyloid A (SAA), haptoglobin (Hp), albumin, butyrylcholinesterase (BChE), insulin-like growth factor1 (IGF1), paraoxonase1 (PON1), total serum thiols (Thiol), glutathione peroxidase (GPox) and total antioxidant capacity determined by different assays, including trolox equivalent antioxidant capacity assessed by two different methodologies (TEAC1/2), ferric reducing ability of plasma (FRAP), and cupric reducing antioxidant capacity (CUPRAC), were determined in serum of 50 queens with spontaneous mammary carcinomas and of 12 healthy female cats. At diagnosis, diseased queens presented significantly higher SAA and Hp, and lower albumin, BChE, GPox, TEAC1, TEAC2 and CUPRAC than controls. Different tumour features influenced concentrations of APP and antioxidants. Increases in serum Hp, and decreases in albumin, Thiol and FRAP were significantly associated with neoplastic vascular emboli, metastasis in regional lymph nodes and/or in distant organs. Distant metastasis development during the course of the disease was associated with increases in SAA and TEAC1. At diagnosis, decreased albumin was associated with a longer survival, and BChE <1.15 μmoL/mL.minute was associated with a shorter survival time on multivariate analysis. Feline malignant mammary tumours are associated with an APP response and oxidative stress, and different tumour features influence the inflammatory response and the oxidative damage. Furthermore, some of these analytes proved to have prognostic value.

Serum amyloid A protein in the course of infectious mononucleosis.

Background:Serum amyloid A (SAA) protein is a major acute phase protein. Increased concentrations have been reported in many inflammatory diseases. In bacterial infections, high levels correlate with those of C-reactive protein (CRP). In viral infections, where CRP changes are weaker, SAA is of value for establishing early diagnosis, monitoring the severity, and the evolution of the disease.Objective:Evaluation of SAA as a marker for diagnosis of infectious mononucleosis, including severe forms.Material and methods:A total of 31 patients with non-complicated and severe, complicated infectious mononucleosis were examined. SAA and CRP were measured by immuniturbidimetric assays at the day of admission and 4.97 ± 1.35 days later.Results:SAA increases significantly than those in a control group, without correlation with the etiologic agent. It decreases when full recovery appears. In the subgroup of subjects with complications, we observed significant increased SAA when Epstein-Barr virus /EBV/ was the etiologic agent, in the course of bacterial and viral secondary infection. SAA is higher than CRP in non-complicated group. In cases of bacterial superinfections, both increase simultaneously and treatment have to be adapted. Second, serum sample for CRP is normal in patients without full recovery where SAA stay increased.Conclusion:In viral infections, high SAA concentrations are indicative for early diagnosis, severe course of the diseases, effect of the treatment, early recovery, and disease outcome. When SAA and CRP increase simultaneously, bacterial co-infection is suspected, and relevant antibiotic treatments have to be initiated.

Identification of Levels of Serum Amyloid A and Apolipoprotein A1 in Serum Proteomic Analysis of Neuropsychiatric Systemic Lupus Erythematosus Patients.

Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) has multiple pathogenic mechanisms that cause diverse manifestations and whose diagnosis is challenging because of the absence of appropriate diagnostic tests. In the present study the application of proteomics using two-dimensional electrophoresis (2D) and mass spectrometry (MS) allowed the comparison of the protein profile of the serum low and high abundance protein fractions of NPSLE patients (NPSLE group) and SLE without neuropsychiatric syndromes (SLE group), Neuropsychiatric syndromes not associated with SLE (NPnoSLE groups), and healthy controls (CTRL group). The gels obtained were digitalized and analyzed with the PDQuest software. The statistical analysis of the spots was performed using the nonparametric Kruskal Wallis and Dunn's multiple comparison tests. Two spots showed significant differences and were identified by MS. Spot 4009 was significantly lower in NPSLE with regard to NPnoSLE (p= 0,004) and was identified as apolipoprotein A1 (APOA1) (score 809-1132). Spot 8001 was significantly higher in NPSLE regarding CTRL and NPnoSLE (p= 0,01 y 0,03, respectively) and was identified as serum amyloid A (SAA) (score 725-2488). The proinflammatory high density lipoproteins (HDL) have been described in SLE. In this HDL the decrease of APOA1 is followed by an increase in SAA. This altered level of both proteins may be related to the inflammatory state that is characteristic of an autoimmune disease like SLE, but this is not specific for NPSLE.

Saponin-based Mycoplasma Bovis Vaccine Containing Lysozyme Dimer Adjuvant Stimulates Acute Phase Response in Calves.

IntroductionMycoplasma bovis is known as a causative agent of many disorders in cattle. In Europe, there is still a lack of commercial vaccines against M. bovis infection. Acute phase response (APR) is a non-specific host reaction to infection, most seen in changes in production of acute phase proteins. The aim of this study was to analyse APR in calves administered with an experimental M. bovis vaccine.Material and MethodsTwelve healthy female calves were divided into two equal groups: experimental and control. The experimental vaccine containing the field M. bovis strain and two adjuvants such as saponin and lysozyme dimer was subcutaneously administered to the experimental group. Phosphate buffered saline was taken as the placebo and given to the control group by the same route as the vaccine. Blood samples were collected prior to the study (day 0), then daily up to day 7, and then each seven days until day 84 post vaccination. The concentrations of serum amyloid A (SAA), haptoglobin (Hp), interferon-γ (IFN-γ), and inteleukin-4 (IL-4) were determined using commercial ELISA kits.ResultsFollowing the vaccination, a significant increase in SAA, Hp, and IFN-γ concentrations was observed when compared to the unvaccinated calves, whereas the IL-4 concentration was not detectable.ConclusionThe experimental saponin-based M. bovis vaccine containing lysozyme dimer adjuvant visibly stimulated the APR in the calves, and some specific cytokines (Th1-dependent) directly involved in this response.

Critical regulation of Th17 cell differentiation by serum amyloid-A signalling in Behcet’s disease

The current understandings on cellular and molecular biology suggest that Th17 axis plays a pivotal role in Behcet’s disease (BD) pathogenesis. Recently the role of serum amyloid-A (SAA) as a potential marker of disease activity in BD patients has been explored, and it has been reported that the occurrence of specific clinical features are significantly associated with high serum levels of this inflammatory mediator. The aim of this study was to investigate the cytokine-like activity of SAA in inducing Th17 differentiation from CD4 + T naive cells in BD. Purified peripheral monocytes from BD and healthy control (HC) were stimulated with SAA “in vitro”, and secreted IL-8, TNF-α, IL-18, IFN-α, IFN-γ, IL-1β and IL-6 were measured using a Bio-Rad multiplex cytokine immunoassay. To assess Th17 differentiation, purified CD4 + T cells were challenged with anti-CD3/CD28 antibodies, while cultured with supernatant derived from SAA stimulated monocytes, and intracellular staining of IL-17A and IFN-γ was evaluated by flow-cytometry. Furthermore, peripheral blood mononuclear cells (PBMCs) were stimulated with SAA and transcript levels of RAR-related orphan nuclear receptor (ROR)–γt and IL-17A were assessed by Real-time PCR. Upon stimulation with SAA, monocytes obtained from both HC and BD groups released large amounts of IL-8, IL-6, TNF-α, IL-1β and IFN-α. Monocytes-derived supernatants from BD patients, but not HC, were capable of promoting Th17 but not Th1 differentiation from CD4 + T cells. However, SAA did not induce up-regulation of Th17 specific mRNA transcript such as IL-17A and (ROR)–γt in PBMCs from both HC and BD. In BD patients SAA induced Th17 polarization rather than Th1 differentiation from CD4 + T cells. These data suggest that a critical regulation of Th17 may be the functional link between acute SAA increase and the induction of Th17 mediated inflammatory response in BD.

Minimal invasiveness of radical laparoscopic prostatectomy:dreams or reality?

To determine the systemic response to extraperitoneal laparoscopic (eLRP) and open retropubic radical prostatectomy (RRP). MATERIALS AND METHODS. In all, 430 patients who had eLRP (200) or open RRP (230) were recruited; patients in both groups had similar preoperative staging. In addition to peri-operative variables (operative duration, complications, blood loss, transfusion rate, hospitalization, catheterization), oncological data (Gleason score, pathological stage, positive margins) were also compared. The extent of the systemic response to surgery-induced tissue trauma was measured in all patients, by assessing the levels of acute-phase markers C-reactive protein (CRP), serum amyloid A (SAA), interleukin-6 (IL-6) and IL-10 before, during and after RP. RESULTS. The duration of surgery, transfusion rate, hospital stay and duration of catheterization were comparable with those of previous studies. There was an increase in IL-6, CRP and SAA but no change in IL-10, and no differences between eLRP and RRP over the entire period assessed. CONCLUSION. The invasiveness of eLRP could not be substantiated objectively on the basis of the variables measured in this study. The surgical trauma and the associated invasiveness of both methods were equivalent.

Serum amyloid A transport across the blood-brain barrier increases with inflammation and is regulated by HDL

Serum amyloid A (SAA) isoforms 1 and 2 are acute phase lipoproteins that are primarily produced by the liver. SAA in blood can increase dramatically during infection, and more modestly during low-grade, chronic systemic inflammation. Nearly all SAA in blood is bound to high-density lipoprotein (HDL). SAA may be an important mediator of neuroinflammation, as its overexpression in the liver causes increase in SAA in the brain, as well as gliosis and depressive-like behavior in mice. We hypothesized that SAA can access the CNS by crossing the blood-brain barrier (BBB), and that HDL modulates SAA transport across the BBB. We first characterized BBB transport kinetics of 125I-labeled SAA1 and 2. 125I-SAA2 crossed the mouse BBB 5x faster than 125I-SAA1, at a rate comparable to that of insulin. Both isoforms completely traversed the BBB and entered brain parenchyma, and transport of both isoforms was not saturable. Both isoforms also rapidly associated with HDL in blood. The transport rate of 125I-SAA2 increased 24 h after a 3 mg/kg injection of lipopolysaccharide independently of BBB disruption. Finally, HDL inhibited SAA transport across the BBB. Therefore, systemic inflammation could contribute to SAA accumulation in the CNS by increasing SAA concentrations in blood, and BBB transport. However, BBB transport of SAA may also be inhibited by HDL, either through HDL binding or competition with other HDL lipoproteins.

Acute-Phase Proteins and Iron Status in Cats with Chronic Kidney Disease.

BackgroundThe role of inflammation in the development and progression of chronic kidney disease (CKD) in cats is not well characterized. Hepcidin is a recently discovered acute‐phase protein (APP) that plays an important role in iron metabolism and contributes to the development of anemia in humans with CKD.ObjectivesTo compare serum APP concentrations, iron status, and erythropoietin (EPO) concentrations in healthy cats and cats with naturally occurring CKD.AnimalsA total of 18 healthy control cats and 38 cats with CKD.MethodsProspective study. After complete physical examination and routine blood analysis, the following tests were performed: serum amyloid A (SAA), haptoglobin (HAP), EPO, serum iron and ferritin concentration as well as total iron‐binding capacity (TIBC). Serum hepcidin‐25 concentration was measured by ELISA kit designed for use in humans.ResultsMean SAA and hepcidin concentrations were significantly higher and mean total iron and TIBC were significantly lower in the CKD group (P < .05). There was a significant positive correlation between serum creatinine concentration (CRT) and 2 of the APPs (SAA and hepcidin; P < .05). Increases in SAA and hepcidin were associated with decreases in TIBC and hematocrit in the CKD group. Fourteen (37%) of the cats with CKD were anemic, and these cats had significantly lower TIBC (P < .05), suggesting a functional iron deficiency. There was no association between survival time and APP, iron status, or EPO concentrations.ConclusionsOur data suggest that CKD in cats is associated with systemic inflammation and altered iron metabolism. With further validation in cats, hepcidin assays may help better characterize these relationships.

Skin inflammation through innate immunity contributes to the elevation of serum amyloid A protein level of psoriatic patients

Serum amyloid A (SAA) is a highly conserved, acute-phase protein synthesized predominantly by the liver, and it has been thought to have a key role in the pathogenesis of rheumatoid arthritis, atherosclerosis, and secondary amyloidosis. We have recently observed that patients with psoriasis (n = 25) have significantly higher level of SAA compared with healthy volunteers (n = 17) or patients with atopic dermatitis (n = 14). Furthermore, the SAA protein level in the sera of patients with psoriasis significantly correlated with Psoriasis Area and Severity Index scores (N = 31, the Spearman rank correlation coefficient = 0.438886, p < 0.01). We next sought molecular mechanisms that might explain a SAA increase in patients with psoriasis and hypothesized that some inflammatory cytokines expressed in psoriatic lesions induce SAA expression in keratinocytes. We stimulated normal human epidermal keratinocytes (NHEKs) with panels of inflammatory cytokines, and the analyses using real-time PCR and ELISA revealed that the Th1 cytokine IFN-gamma (50 ng/ml) and the Th17 cytokine IL-17A (50 ng/ml) significantly induced SAA expression in NHEKs, but the Th2 cytokines IL-4 (50 ng/ml) and IL-13 (50 ng/ml) did not. Furthermore, SAA induced SAA itself and IL-36 gamma expression in a dose-dependent manner (10−8–10−6 M) in NHEKs, and siRNA-mediated gene silencing clarified that the inductions were mediated by Toll-like receptor 2. These results suggest that psoriatic skin inflammation would contribute to the elevation of SAA in the sera of psoriasis patients, which might trigger systemic complications.