Analysis of serum amyloid A in sarcoidosis patients

A crucial pathogenetic role of serum amyloid A (SAA) in granulomatous inflammation of sarcoidosis has recently been reported. In this study we analyzed SAA expression in detail, starting from proteomic analysis of serum of sarcoidosis patients. We also used the faster ELISA method that enabled us to examine a greater number of samples. Serum concentrations of SAA were significantly higher in sarcoidosis patients than controls (p<0.001), inversely correlated with FEV(1) and significantly higher in patients with subacute onset requiring prolonged and multiple steroid treatments (class 6 SCAC) than in patients with subacute onset not requiring therapy (class 4 SCAC) (p<0.001). Our results suggest that serum amyloid A could be a suitable marker of sarcoidosis: its serum concentrations are significantly higher in sarcoidosis patients than controls, the protein is only expressed in gels of sarcoidosis patients and not in healthy subjects, and the SAA1 isoforms could match the unidentified biomarker of sarcoidosis reported in a previous proteomic study by another group. The effectiveness of SAA as a clinical biomarker of sarcoidosis should now be investigated in a large prospective study.     

血清淀粉样蛋白A1基因多态性对汉族人群颈动脉内中膜厚度的影响

Objective To explore the association between genetic polymorphism of serum amyloid protein A1 (SAA1) with carotid intima media thickness in a healthy Han Chinese population of Xinjiang. Methods A total of 449 healthy Han Chinese participating the cardiovascular risk survey between June 2007 and September 2009 were included, the genotypes of the SAA1 were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The mean IMT of the right and left common carotid arteries were measured by B-mode ultrasonography. Results (1) There was strong linkage disequilibrium between rs12218 and rs2229338 (D'=0. 89). (2) The carotid common IMT (CC-IMT) and the carotid bulb IMT (CB-IMT) were similar between the AA genotype (wild genotype) and the GGFAG genotype (mutational genotype) in rs2229338 of SAA1 gene. (3) CC-IMT[(0.081 ±0.071)cm vs (0.068 ±0. 019 ) cm, P = 0. 01] was significantly thicker in CC + CT genotype ( mutational genotype) group than in TT genotype (wild genotype) of rs12218 group and the difference remains significant after adjustment for age,gender,blood pressure, waist circumference, creatinine and high density lipoprotein cholesferoL CB-IMT [(0.085±0. 038)cm vs. (0.081 ± 0. 052) cm,P =0. 36] was similar between CC +CT genotype and TT genotype of rs12218 groups. Conclusion Our results suggested that the genetic polymorphism of SAA1 might be linked with IMT and rs12218 mutation could serve as a promoting factor for IMT in Han Chinese people.     

血清淀粉样蛋白A1基因多态性对汉族人群颈动脉内中膜厚度的影响

Objective To explore the association between genetic polymorphism of serum amyloid protein A1 (SAA1) with carotid intima media thickness in a healthy Han Chinese population of Xinjiang. Methods A total of 449 healthy Han Chinese participating the cardiovascular risk survey between June 2007 and September 2009 were included, the genotypes of the SAA1 were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The mean IMT of the right and left common carotid arteries were measured by B-mode ultrasonography. Results (1) There was strong linkage disequilibrium between rs12218 and rs2229338 (D'=0. 89). (2) The carotid common IMT (CC-IMT) and the carotid bulb IMT (CB-IMT) were similar between the AA genotype (wild genotype) and the GGFAG genotype (mutational genotype) in rs2229338 of SAA1 gene. (3) CC-IMT[(0.081 ±0.071)cm vs (0.068 ±0. 019 ) cm, P = 0. 01] was significantly thicker in CC + CT genotype ( mutational genotype) group than in TT genotype (wild genotype) of rs12218 group and the difference remains significant after adjustment for age,gender,blood pressure, waist circumference, creatinine and high density lipoprotein cholesferoL CB-IMT [(0.085±0. 038)cm vs. (0.081 ± 0. 052) cm,P =0. 36] was similar between CC +CT genotype and TT genotype of rs12218 groups. Conclusion Our results suggested that the genetic polymorphism of SAA1 might be linked with IMT and rs12218 mutation could serve as a promoting factor for IMT in Han Chinese people.     

血清淀粉样蛋白A在呼吸系统疾病中的研究进展

血清淀粉样蛋白A(serum amyloid A,SAA)是一个非常敏感的急性时相蛋白.研究发现SAA与C-反应蛋白相比,其灵敏度、特异度更高,尤其病毒感染时其血清水平显著升高,而C-反应蛋白血清水平基本正常或轻度升高.其研究涉及呼吸系统多种疾病,如:上呼吸道感染、急性气管-支气管炎、肺炎、慢性阻塞性肺疾病、肺癌、过敏性鼻炎和支气管哮喘、肺结核、肺囊性纤维化、肺结节病;此外在淀粉样变性、自身免疫性疾病,移植及心血管疾病中也有广泛研究.     

Immune infiltration-associated serum amyloid A1 predicts favorable prognosis for hepatocellular carcinoma

BACKGROUND Serum amyloid A1(SAA1) is an acute-phase protein involved in acute or chronic hepatitis. Its function is still controversial. In addition, the effect of the expression of SAA1 and its molecular function on the progression in hepatocellular carcinoma(HCC) is still unclear.AIM To demonstrate the expression of SAA1 and its effect on the prognosis in HCC and explain further the correlation of SAA1 and immunity pathways.METHODS SAA1 expression in HCC was conducted with The Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC) in GEPIA tool, and the survival analysis based on the SAA1 expression level was achieved in the Kaplan-Meier portal. The high or low expression group was then drawn based on the median level of SAA1 expression. The correlation of SAA1 and the clinical features were conducted in the UALCAN web-based portal with TCGA-LIHC, including tumor grade, patient disease stage, and the TP53 mutation. The correlation analysis between SAA1 expression and TP53 mutation was subjected to the TCGA portal. The tumor purity score and the immune score were analyzed with CIBERSORT. The correlation of SAA1 expression and tumor-infiltrating lymphocytes was achieved in TISIDB web-based integrated repository portal for tumor-immune system interactions. GSE125336 dataset was used to test the SAA1 expression in the responsive or resistant group with anti-PD1 therapy. Gene set enrichment analysis was applied to evaluate the gene enrichment signaling pathway in HCC. The similar genes of SAA1 in HCC were identified in GEPIA, and the proteinprotein interaction of SAA1 was conducted in the Metascape tool. The expression of C-X-C motif chemokine ligand 2, C-C motif chemokine ligand 23, and complement C5 a receptor 1 was studied and overall survival analysis in HCC was conducted in GEPIA and Kaplan-Meier portal, respectively.RESULTS SAA1 expression was decreased in HCC, and lower SAA1 expression predicted poorer overall survival, progression-free survival, and disease-specific survival. Furthermore, SAA1 expression was further decreased with increased tumor grade and patient disease stage. Also, SAA1 expression was further downregulated in patients with TP53 mutation compared with patients with wild type TP53. SAA1 expression was negatively correlated with the TP53 mutation. Lower SAA1 predicted poorer survival rate, especially in the patients with no hepatitis virus infection, other than those with hepatitis virus infection. Moreover, the SAA1 expression was negatively correlated with tumor purity. In contrast, SAA1 expression was positively correlated with the immune score in HCC, and the correlation analysis between SAA1 expression and tumor-infiltrating lymphocytes also showed a positive correlation in HCC. Decreased SAA1 was closely associated with the immune tolerance of HCC. C-X-C motif chemokine ligand 2 and C-C motif chemokine ligand 23 genes were identified as the hub genes associated with SAA1, which could also serve as favorable prognosis markers for HCC.CONCLUSION SAA1 is downregulated in the liver tumor, and it is closely involved in the progression of HCC. Lower SAA1 expression indicates lower survival rate, especially for those patients without hepatitis virus infection. Lower SAA1 expression also suggests lower immune infiltrating cells, especially for those with immune cells exerting anti-tumor immune function. SAA1 expression is closely associated with the anti-tumor immune pathways.     

血清淀粉样蛋白A水平与冠状动脉粥样硬化的研究进展

冠状动脉粥样硬化性心脏病，简称“冠心病”，是一种危害全球公民健康的主要疾病。所以早期识别相关生物学标志物是做到对疾病早诊断、早治疗的关键。血清淀粉样蛋白A是一种由肝脏合成的急性期蛋白，属于炎性标志物。近年来大量研究发现SAA与冠心病的发生发展存在明显的关联性。因此，本文就近年来关于SAA与冠心病的相关性的研究成果做进一步综述。     

Glycation impairs high-density lipoprotein function

Aims/hypothesis. To examine the effects of incubation of high-density lipoprotein (HDL) under hyperglycaemic conditions on several functions of HDL in vitro.¶Methods. Human HDL (5 mg protein) was incubated for 1 week at 37 °C in the presence or absence of 25 mmol/l glucose. Additional samples of human HDL were incubated in butylated hydroxytoluene to control for oxidation.¶Results. High-density lipoprotein incubated for 1 week in 25 mmol/l glucose had significant increases in the glycation product, fructoselysine and in the advanced glycation end product, N ?-(carboxymethyl)-lysine. High-density lipoprotein apolipoprotein AI and AII concentrations were not altered but glycated HDL had a 65 % reduction in paraoxonase enzymatic activity. Glycated HDL did not inhibit monocyte adhesion to human aortic endothelial cells in response to oxidised low-density lipoprotein in vitro (43 ± 4 monocytes bound vs 21 ± 2 monocytes for control HDL, p < 0.0001). Hepatic lipase-mediated non-esterified fatty acid release from HDL lipids was enhanced in glycated HDL compared with control HDL (25 ± 1 vs 16 ± 1 nmol non-esterified fatty acid hydrolysed/min, respectively, p < 0.0001). Direct glycation of purified paraoxonase protein by incubation in 25 mmol/l glucose caused a 40 % reduction in enzymatic activity. This glycated paraoxonase did not inhibit monocyte adhesion to human aortic endothelial cells in vitro (68 ± 3 monocytes vs 49 ± 2 monocytes bound for control paraoxonase, respectively, p < 0.001). We also measured a 40 % reduction in paraoxonase activity in patients with Type II (non-insulin-dependent) diabetes mellitus and documented coronary artery disease compared with non-diabetic subjects, p < 0.0001.¶Conclusions/interpretation. Alterations in function of HDL caused by exposure to hyperglycaemic conditions could contribute to the accelerated atherosclerosis observed in Type II diabetes. [Diabetologia (2000) 43: 312–320]     

A short-term increase in dietary cholesterol and fat intake affects high-density lipoprotein composition in healthy subjects

Background and Aims

High-cholesterol and high-fat diets alter biochemical composition and anti-oxidant properties of high-density lipoproteins (HDL) in animals. Whether this occurs in humans is unknown. Therefore, we examined the effect of a short-term elevation in dietary cholesterol and fat intake on HDL composition in healthy subjects.

低水平高密度脂蛋白——冠心病独立危险因素

许多临床资料、流行病学研究发现,高密度脂蛋白与冠心病事件的发生率呈负相关,且支持低水平高密度脂蛋白是冠心病的独立危险因素。低水平高密度脂蛋白患者经药物治疗可以明显减少冠心病事件的发生率。     

The path of murine serum amyloid a through peritoneal macrophages

Serum amyloid A (SAA) is a family of proteins encoded by four related genes. Of the four, isoforms 1.1 and 2.1 are acute phase proteins synthesized by the liver. They become major components of the HDL plasma fraction during acute tissue injury and the HDL/SAA complex is readily taken up by macrophages. Herein we investigated the path SAA follows when presented to macrophages as HDL/SAA or in liposomes. Using antibodies specific to SAA and confocal microscopy, or EM autoradiography where only SAA is radio-labeled, we show that HDL/SAA is taken up rapidly by macrophages and within 30 min SAA, or fragments thereof, proceeds through the cytoplasm to the peri-nuclear region and then the nucleus. Within 45–60 min SAA, or fragments thereof, is found back in the cytoplasm and at the plasma membrane where it is subsequently extruded. The observation that SAA, or fragments thereof, traverse the nucleus is a novel finding and may implicate SAA in macrophage gene regulation. It also raises questions by what mechanism SAA enters and leaves the nucleus. We further investigated if both SAA isoforms traffic through the macrophage in a similar manner. Isoform differences were observed. Both isoforms bind well to the plasma membrane of macrophages at 4°C, but at 37°C only SAA2.1 is taken up by the cell in significant quantity, and is observed in the nucleus, suggesting that the two isoforms are handled differently and that they may have discrete physiological roles.     

高密度脂蛋白胆固醇及其相关因子载脂蛋白A-I和血清淀粉样蛋白A与非糖尿病性冠心病的关系

目的 观察高密度脂蛋白胆固醇(HDL-c)相关因子载脂蛋白A-I(apoA-I)和血清淀粉样蛋白A(SAA)对非糖尿病性冠心病的影响.方法 应用酶联免疫吸附法分别检测冠心病组(94例)及对照组(86例)患者血浆中apoA-I和SAA,观察HDL-C,apoA-I及SAA和冠心病发病之间的关系,并与人口学因素、血脂和炎症...     

血清淀粉样蛋白A与冠心病的相关性研究

目的 调查广州市石牌村老年人群血清淀粉样蛋白A（amyloid A,SAA）水平与冠心病之间的关系。方法 从该村原居民老年人群血清标本950份,随机抽取161份,应用酶联免疫吸附法测量其SAA水平。将其分为有冠心病史组（22例）与无冠心病史组（139例）。按SAA水平分为低中高3组。结果 有冠心病史组SAA水平3106μg／L（ng／ml）,95％置信区间291～5897μg／L;而无冠心病史组SAA水平756μg／L,95％置信区间184～3100μg／L,差异有统计学意义（P＜0.01）。SAA水平与冠心病的Logistic回归分析表明：随着SAA水平逐渐升高,冠心病危险性亦有显著性增加。结论 SAA水平与冠心病呈正相关。     

血清淀粉样蛋白A在类风湿关节炎患者体内表达的研究

目的 通过检测血清淀粉样蛋白A(SAA)在类风湿关节炎(RA)患者血清、关节液及滑膜中的表达,探讨其在RA发病机制中的作用.方法 采用酶联免疫吸附试验(ELISA)分别检测RA、骨关节炎患者和健康对照人群血清以及RA与骨关节炎患者关节液中SAA的水平;蛋白印迹法测定SAA在血清中的表达;免疫组织化学技术检测RA和骨关节炎滑膜中SAA的表达.应用t检验或Kruska-Wallis秩和检验进行统计分析.结果 RA血清中SAA含量[(318±132) μg/L]显著高于骨关节炎[(127±47) μg/L]和健康对照组[(127±41) μg/L,P均＜0.01].RA关节液中SAA含量[(571±473) μg/L]显著高于骨关节炎[(129±33) μg/L,t=2.46,P=0.04].蛋白印迹法结果显示各组血清样品中均有SAA条带;RA的SAA表达明显高于其他2组.病理结果显示SAA在RA关节滑膜高表达,位于血管内皮细胞、滑膜成纤维细胞、巨噬细胞以及血管周围;在骨关节炎,SAA仅见于关节血管周围和成纤维细胞.结论 RA血清和关节液中SAA的含量显著增高;SAA在RA滑膜组织中高表达,且表达位置与骨关节炎有明显差别,提示SAA可能参与了RA的炎症反应和关节损害.     

Discriminative value of serum amyloid A and other acute-phase proteins for coronary heart disease

We studied the value of serum amyloid A (SAA), a first-class acute-phase protein, as a marker for coronary heart disease (CHD) in a middle-aged male population. In a working population of 16 307 men (age, 35–59 years), 446 cases had a history of CHD or prominent Q:QS waves on electrocardiogram. For each case, two matched controls were investigated. SAA, measured by immunonephelometry, was correlated with other acute-phase proteins, cardiovascular risk factors, and infectious serology markers. SAA concentrations were significantly higher in the cases than in controls (P<0.05) and correlated with serum C-reactive protein (CRP) (r=0.61), plasma fibrinogen (r=0.39), serum haptoglobin (r=0.26), and body mass index (r=0.13) (P<0.001). Serum CRP is a better marker for CHD than SAA, which showed discriminative power only in a univariate model comparing highest versus lowest tertile (odds ratio, 1.39; 95% confidence interval, 1.03–1.87). Neither SAA nor other acute-phase proteins correlated with Chlamydia pneumoniae immunoglobulin (Ig)G, Helicobacter pylori IgG and IgA, and cytomegalovirus IgG. In conclusion, although SAA has a discriminative value for CHD, serum CRP is to be preferred as a first-class acute-phase reactant for detection of the disease.     

血清淀粉样蛋白A1基因多态性对汉族人群颈动脉内中膜厚度的影响

目的 探讨血清淀粉样蛋白A1(SAA1)基因多态性对颈动脉内中膜厚度(IMT)的影响.方法资料来源于2007至2010年"新疆维吾尔自治区不同民族心血管疾病危险因素调查研究"数据,人选其中健康汉族人群449例,采用限制性片段长度多态性(RFLP)方法对SAA1基因rs2229338和rs12218进行分型.彩色超声检测颈总动脉干部内中膜厚度(CC-IMT)和膨大部内中膜厚度(CB-IMT),分析不同基因型之间颈动脉IMT的差异.结果 (1)rs2229338和rs12218存在强连锁不平衡(D'=0.89).(2)SAA1基因rs2229338突变型(GG+AG)与野生型(AA)的CC-IMT和CB-IMT值差异均无统计学意义.(3)SAA1基因rs12218突变型(CC+CT)CC-IMT值大于野生型(TT)[(0.081±0.071)cm比(0.068±0.019)cm,P=0.01],在校正年龄、性别、血压、腰围、肌酐和高密度脂蛋白胆固醇的影响后,差异仍具有统计学意义(P=0.04);rs12218突变型(CC+CT)与野生型(TT)的CB-IMT值差异无统计学意义[(0.085±0.038)cm比(0.081±0.052)cm,P=0.36].结论在新疆维吾尔自治区汉族人群,SAA1基因多态性和颈动脉IMT存在关联,rs12218突变型基因可能会增加颈动脉IMT.

Abstract：

Objective To explore the association between genetic polymorphism of serum amyloid protein A1 (SAA1) with carotid intima media thickness in a healthy Han Chinese population of Xinjiang. Methods A total of 449 healthy Han Chinese participating the cardiovascular risk survey between June 2007 and September 2009 were included, the genotypes of the SAA1 were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The mean IMT of the right and left common carotid arteries were measured by B-mode ultrasonography. Results (1) There was strong linkage disequilibrium between rs12218 and rs2229338 (D'=0. 89). (2) The carotid common IMT (CC-IMT) and the carotid bulb IMT (CB-IMT) were similar between the AA genotype (wild genotype) and the GGFAG genotype (mutational genotype) in rs2229338 of SAA1 gene. (3) CC-IMT[(0.081 ±0.071)cm vs (0.068 ±0. 019 ) cm, P = 0. 01] was significantly thicker in CC + CT genotype ( mutational genotype) group than in TT genotype (wild genotype) of rs12218 group and the difference remains significant after adjustment for age,gender,blood pressure, waist circumference, creatinine and high density lipoprotein cholesferoL CB-IMT [(0.085±0. 038)cm vs. (0.081 ± 0. 052) cm,P =0. 36] was similar between CC +CT genotype and TT genotype of rs12218 groups. Conclusion Our results suggested that the genetic polymorphism of SAA1 might be linked with IMT and rs12218 mutation could serve as a promoting factor for IMT in Han Chinese people.     

淀粉酶联合CRP和SAA检测对急性胰腺炎诊断价值的评价

目的 探讨淀粉酶、C反应蛋白(C-reactive protein,CRP)及血清淀粉样物质A(serumamyloid A,SAA)的变化对AP诊断的临床意义.方法 测定MAP和SAP患者发病24 h内、48 h、72 h及第7天的血、尿淀粉酶和CRP、SAA水平.结果 发病24 h内SAP患者的血淀粉酶、尿淀粉酶、CRP和SAA水平分别为(904.5±402.2)U/L、(2280.3±1270.3)U/L、(155.6±36.2)mg/L和(521.9±109.4)mg/L,均明显高于MAP患者的(598.3±400.4)U/L、(1304.9±868.7)U/L、(51.9 4±38.0)mg/L和(158.6±187.6)mg/L(P＜0.05或P＜0.001);血淀粉酶高峰出现于发病后24 h内,而尿淀粉酶、CRP和SAA高峰出现在发病48 h,分别为(2173.5±1110.6)U/L、(185.3±41.4)mg/L和(717.5±144.2)mg/L.MAP和SAP患者血、尿淀粉酶水平在第7天均明显降低(P＜0.05),MAP患者CRP、SAA在第7天也明显降低(P＜0.05),但SAP患者CRP、SAA在第7大无明显降低(P＞0.05).CRP、SAA和病变发展相平行,CRP和SAA呈正相关(r=0.761,P＜0.05).结论 淀粉酶联合CRP、SAA水平的检测能够早期诊断AP,CRP和SAA可作为早期诊断SAP的参考指标.     

Serum amyloid A in patients with idiopathic pulmonary fibrosis

BackgroundSerum amyloid A (SAA) is an apo-lipoprotein (12–14 kDa) produced by the liver in response to proinflammatory cytokines from activated monocytes. The precursor of SAA is an acute-phase protein involved in the pathogenesis of sarcoidosis and has been found to be increased during exacerbation of chronic obstructive pulmonary disease and lung cancer. However, no data are available on SAA levels in patients with idiopathic pulmonary fibrosis (IPF), the most common and severe idiopathic form of interstitial pneumonitis associated with a usual interstitial histological and radiological pattern. The aim of this preliminary study was to evaluate SAA concentration in patients with IPF and to explore its potential use as a clinical biomarker.MethodsSAA levels were determined by enzyme-linked immunosorbent assay in a population of 21 patients with IPF (14 male, aged 64.8 ± 8.1 years) and compared with those in 11 healthy controls (3 male, aged 55 ± 11.3 years). Clinical, functional, and immunological data were collected in a database.ResultsSAA levels were significantly higher in patients with IPF than in controls (p = 0.03). In patients with IPF, statistically significant correlations were found between SAA and HDL cholesterol levels (r = ?0.62, p = 0.05) and FVC % predicted value (r = ?0.52, p = 0.01).ConclusionsSAA is a promising marker of disease severity in patients with IPF. Our preliminary data suggest a potential pathogenetic role of alteration in lipid metabolism in this rare disease.     

血清淀粉样蛋白A促进动脉粥样硬化形成机制研究进展

血清淀粉样蛋白A作为急性反应时相蛋白在动脉粥样硬化的形成过程中有明显的促进作用。血清淀粉样蛋白A通过刺激炎症因子的释放导致炎症的产生,与脂蛋白结合改变高密度脂蛋白的生理功能,引发血管内皮和平滑肌功能障碍,还会引起血栓形成,这些都促进动脉粥样硬化的发生发展。     

炎性因子对急性冠状动脉综合征的早期预测价值

目的:观察冠心病不同类型患者中血清炎性递质C反应蛋白(CRP)、淀粉样蛋白A(SAA)和白细胞介素-6(IL-6)水平的变化以及炎症递质之间的关系,探讨急性冠状动脉综合征(ACS)预测的炎症指标。方法:用酶联免疫吸附法检测了32例急性心肌梗死,30例不稳定型心绞痛,20例稳定型心绞痛和16例健康对照者血清CRP、SAA、IL-6水平,并比较上述指标与不同类型冠心病,ACS与非ACS之间的关系。结果:ACS患者血清CRP、SAA和IL-6均高于非ACS患者,分别为(6.94±4.56)∶(2.48±2.32)mg/L;(217.23±441.14)∶(18.18±28.05)mg/L;(4.37±6.35)∶(1.31±0.98)ng/L(均P<0·01)。CRP、SAA和IL-6三者之间呈显著正相关。以CRP、SAA和IL-6的x-±2s为截断值联合预测ACS的灵敏度为73.8%,特异度为91.7%,准确性为80.4%。结论:ACS患者血清SAA、CRP、IL-6水平升高,提示与ACS的发生有关,是动脉粥样硬化斑块不稳定的标志,可以作为ACS的早期辅助诊断指标。