血清淀粉样蛋白A与呼吸系统疾病的研究进展

<正>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(acute phase protein,APP)。研究发现在许多炎症性疾病,血浆SAA水平显著升高。以往研究证实SAA是淀粉样蛋白A(amyloid A,AA)的前体[1],但SAA的生物学功能仍不十分清楚。近年来研究发现SAA是一个炎症标志物,特异性及敏感性均高于C-反应蛋白(C-re-     

血清淀粉样蛋白A与慢性疾病关系的研究进展

血清淀粉样蛋白A(serum amyloid A，SAA)是由位于人11号染色体上的同一簇基因（在人类只有SAA1,SAA2,SAA4表达）编码的一族由104个氨基酸组成多形性蛋白，天然状态下分子量大约在12000～14000，主要在白色脂肪组织和肝细胞合成。SAA是载脂蛋白和高密度脂蛋白颗粒的组成成分，是人类和多种哺乳动物主要的急性期蛋白之一。在炎性和创伤的刺激下，血清中SAA1和SAA2可在5～6 h内迅速升高100～1000倍，因而两者被合称为急性时相SAA。根据既往研究报道，SAA是目前较为敏感的炎性反应物之一，常作为一些疾病炎性反应活跃性和疗效判断的有效指标，被广泛应用于临床。现就SAA与多种慢性疾病关联的研究进展做一概述。     

血清淀粉样蛋白A与动脉粥样硬化关系的研究进展

以动脉粥样硬化(AS)为病理基础的冠心病是当今危害人们生命健康的重要疾病。由细胞因子介导的炎症反应可能在AS过程中扮演着重要的角色。血清淀粉样蛋白A(SAA)是一种急性时相蛋白,在急性反应期水平上升极快,并引起所有急性期反应蛋白总量的急剧增加,这种特性使得SAA成为目前最敏感的炎症标志物之一。SAA的血浆浓度变化是否与AS的病变程度相关?1SAA的分子结构、基因表达及代谢SAA主要来源于肝脏,肝细胞是SAA合成部位。人类的某些正常或异常组织中的上皮细胞也能表达某些类型的SAA〔1〕。SAA主要由白细胞介素(IL)-1、IL-6和肿瘤…     

血清淀粉样蛋白A对脑动脉粥样硬化性狭窄影响的研究进展

血清淀粉样蛋白A（serum amyloid A，SAA）存在于各种哺乳动物和禽类的体内，其合成的部位主要在肝脏，由同一簇基因编码的一组多形性蛋白组成。SAA家族包含不同表达形式的载脂蛋白、急性相蛋白A（acute—phase serum amyloid A，A—SAA）和结构型SAA（constitutive serum amyloid A，C—SAA）。正常人血清SAA值为0—0．78mg／L。当机体受到各种炎性反应因素刺激时，     

肺癌患者血清淀粉样蛋白A(SAA)水平及临床意义

正近年来,我国肺癌发病率和死亡率大幅增长,严重威胁人群健康及生命安全,多数患者就诊时已处于中晚期,临床治疗效果较差,预后不良。血清淀粉样蛋白A(SAA)是一种与血浆高密度脂蛋白(HDL)相结合的急性相蛋白,主要来源于脂肪细胞、肝脏细胞及肿瘤细胞[1]。SAA被认为是与机体炎症反应相关的蛋白。最近研究表明,SAA在恶性肿瘤的发生发展过程中,尤其是在肿瘤的侵袭或转移过程中起到重要作用[2]。研究发现,SAA能够抑制肿瘤细     

支气管扩张和支气管癌的急性期反应

C-反应性蛋白(CRP)和血清淀粉样A-蛋白(SAA)是人体在损伤,感染或肿瘤形成时的急性期反应物。SAA多与高密度脂蛋白有关,是淀粉样A的前体,在继发性全身性淀粉样变性中可形成     

血清淀粉样蛋白A--类风湿关节炎的一个炎性指标

目的 研究血清淀粉样蛋白－A（SAA）在类风湿关节炎（RA）中的临床意义。方法 对80例RA，采用ELISA法进行SAA定量测定，采用全自动速率散射比浊法进行CRP及RF定量或半定量测定。结果 RA患者的SAA浓度，病情活动组比非活动组明显增加；活动组经治疗，SAA浓度下降至正常范围；SAA的变化趋势与CRP、ESR变化趋势相似。结论 RA患者血清SAA浓度可能是一个病情活跃及疗效判断的替代指标。     

血清SAA与2型糖尿病关系的研究进展

血清淀粉样蛋白A（SAA）是一种主要由肝细胞合成的多基因编码的蛋白家族,由104个氨基酸组成的多肽,是人类和哺乳动物主要的急性期蛋白。糖尿病是一种自身免疫介导的低度炎症性疾病。SAA作为促炎性细胞因子,在糖尿病及其合并症的发生、发展过程中起重要作用。现将其与糖尿病关系的研究进展综述如下。     

SAA在鼻咽癌CNE-2细胞中的表达及其对细胞生长、凋亡的影响

目的 观察血清淀粉样蛋白A(SAA)在鼻咽癌CNE-2细胞中的表达及其对细胞生长、凋亡的影响.方法 构建针对SAA基因的shRNA表达干扰载体,筛选出有效的小干扰RNA(siRNA)序列,利用siRNA技术和高表达载体分别沉默及过表达SAA,检测SAA表达对鼻咽癌CNE-2细胞的生长及凋亡的影响.结果 pGPU6/GFP/Neo-SAA1-homo-482和pCD3.1(+)-SAA在鼻咽癌CNE-2细胞中可有效地沉默及过表达SAA基因的mRNA和蛋白,且与对照组比较差异具有统计学意义(P均＜0.05);SAA增高可促进鼻咽癌CNE-2细胞生长,降低可促进鼻咽癌CNE-2细胞凋亡.结论 在SAA基因的shRNA表达干扰载体中,只有pGPU6/GFP/Neo-SAA1-homo-482可有效沉默SAA在鼻咽癌CNE-2细胞中的表达;SAA增高可促进鼻咽癌CNE-2细胞生长,SAA沉默可促进鼻咽癌CNE-2细胞凋亡.     

急性后循环缺血性脑卒中患者血清淀粉样蛋白A和C反应蛋白浓度变化

目的观察急性缺血性脑卒中患者发病早期血清淀粉样蛋白A(SAA)、C反应蛋白(CRP)浓度变化。方法对88例前循环缺血性脑卒中患者、87例后循环缺血性脑卒中患者和88例健康对照者进行研究,采用酶联免疫吸附试验测定SAA含量,免疫散射比浊法检测CRP含量。结果 SAA、CRP含量在前循环缺血性脑卒中组、后循环缺血性卒中组和对照组之间差异有统计学意义(P均0.05),SAA与CRP显著呈正相关。结论后循环缺血性卒中患者SAA、CRP水平较高,炎症反应较强。     

Response of C-reactive protein and serum amyloid A to influenza A infection in older adults

Influenza epidemics are associated with significant morbidity and mortality in the elderly, with a substantial proportion of deaths due to cardiovascular events. Elevations of acute-phase proteins have been associated with an increased risk of atherosclerotic events. Therefore, serum amyloid A (SAA) and C-reactive protein (CRP) were measured during influenza illness and 4 weeks later in 7 young persons, 15 elderly outpatients, and 36 hospitalized adults. Striking elevations were seen in mean acute SAA and CRP levels in all groups, but hospitalized patients had the highest levels (SAA, 503 vs. 310 microg/mL [P=.006]; CRP, 120 vs. 34 microg/mL [P<.001]). The presence of dyspnea, wheezing, and fever was also associated with high CRP levels. Influenza infection is associated with significant elevations of SAA and CRP levels in elderly patients, especially those who require hospitalization. It is possible that direct effects of CRP may exacerbate preexisting atherosclerotic lesions and may help explain cardiovascular events associated with acute influenza.     

N-terminal sequence analysis of SAA-derivatives purified from murine inflammatory macrophages.

The pathogenesis of secondary amyloidosis in vivo is not well-understood. Experimental studies suggest that incomplete degradation of acute phase serum amyloid A (SAA), presumably endocytosed by activated monocytoid cells, may lead to intralysosomal formation of amyloid A (AA). To establish a possible link between these two events, we have carried out partial N-terminal sequence analysis of affinity purified SAA derivatives from peritoneal macrophages isolated at 4 weeks post-infection from alveolar hydatid cyst infected C57BL/6 mice. The macrophage lysates yielded five N-terminally intact SAA derivatives of approximately 5 to approximately 12 kDa which reacted with anti-mouse AA IgG, and contained a mixture of SAA1 and SAA2 isoforms. The SAA2:SAA1 ratio, evaluated from their proportion present in each M(r) SAA derivative, showed a decrease with the decreasing apparent mass of the N-terminally infected SAA material. These results not only confirm that both SAA1 and SAA2 are processed by activated monocytoid cells but, more importantly, establish a plausible link between N-terminally intact SAA derivatives and formation of AA within activated monocytoid cells.     

支架成形术与药物治疗重度颅内动脉狭窄的长期疗效对比

目的探讨重度颅内动脉粥样硬化性狭窄（ICAS）的支架成形术（SAA）与单纯药物治疗的长期疗效。方法回顾性分析2009年12月-2012年3月ICAS致短暂性脑缺血发作或脑梗死人院208例患者的临床资料,根据患者的选择分为SAA组（均用Wingspan支架）122例,药物治疗组86例。神经功能改善率以治疗前后美国国立卫生研究院卒中量表（NIHSS）评分差值／治疗前NIHSS评分的比值评价。主要终点事件为30d内出现的脑血管事件和死亡,次要终点事件为30d后责任血管相关缺血性脑血管事件。比较两组患者的围手术期并发症,再发脑血管事件、死亡等随访结果。结果每3个月随访1次,随访4-36个月,平均（19．3±1．7）个月。①SAA组30d,6、12、18、24个月的神经功能改善率分别为4．9％、45．1％、57．4％、53．3％和55．0％;药物组为3．5％、26．7％、20．9％、24．4％和23．2％,两组30d后的神经功能改善率差异有统计学意义（P〈0．01）。②SAA组手术成功率为98．4％。术后30d内,SAA组共有4例发生围手术期严重并发症,另有2例症状轻微。药物组30d内有2例（2．3％）发生狭窄动脉区轻微卒中;30d内两组的主要终点事件发生率差异无统计学意义。③SAA组30d后责任血管发生缺血事件为7例（5．7％）,药物组为15例（17．4％）出现责任血管缺血性脑血管事件,两组次要终点事件发生率差异有统计学意义（P〈0．01）。结论血管内SAA治疗ICAS较为安全,在预防责任血管相关的缺血性脑血管事件与改善神经功能方面,长期疗效优于内科药物治疗。     

A serum amyloid A and LDL complex as a new prognostic marker in stable coronary artery disease

BACKGROUND: Although some reports have indicated that acute phase proteins such as C-reactive protein (CRP) and serum amyloid A (SAA) can predict the prognosis in patients with acute coronary syndrome, the value of these markers in patients with stable coronary artery disease (CAD) still remains obscure. Therefore, our aim was to determine the prognostic value of inflammatory markers in patients with stable coronary artery disease. METHODS AND RESULTS: We conducted a prospective cohort study in 140 consecutive patients with stable coronary artery disease who had at least one coronary stenosis more than 50% in diameter seen on diagnostic coronary angiography (CAG). We determined serum levels of the SAA/LDL complex as a new marker in addition to CRP and SAA. Serum levels of the SAA/LDL complex were measured by a sandwich enzyme-linked immunosorbent assay (ELISA). End-points were defined as cardiac death, myocardial infarction, cerebral infarction, and coronary revascularization. End-point events occurred in 21 patients (2 death from myocardial infarction, 2 cerebral infarction, and 17 revascularization). Age (year) (OR = 1.14, CI: 1.05-1.25), diabetes mellitus (OR = 3.50, CI: 1.08-11.40), triglyceride (10mg/dl) (OR = 1.12, CI: 1.01-1.23) and SAA/LDL complex (10 microg/ml) (OR = 2.32, CI: 1.05-4.70) were independently related to the events. A reconstitution experiment suggested that the SAA/LDL complex is derived by oxidative interaction between SAA and lipoproteins. CONCLUSIONS: The SAA/LDL complex reflects intravascular inflammation directly and can be a new marker more sensitive than CRP or SAA for prediction of prognosis in patients with stable coronary artery disease.     

Pathogenetic mechanisms of amyloid A amyloidosis

Systemic amyloid A (AA) amyloidosis is a serious complication of chronic inflammation. Serum AA protein (SAA), an acute phase plasma protein, is deposited extracellularly as insoluble amyloid fibrils that damage tissue structure and function. Clinical AA amyloidosis is typically preceded by many years of active inflammation before presenting, most commonly with renal involvement. Using dose-dependent, doxycycline-inducible transgenic expression of SAA in mice, we show that AA amyloid deposition can occur independently of inflammation and that the time before amyloid deposition is determined by the circulating SAA concentration. High level SAA expression induced amyloidosis in all mice after a short, slightly variable delay. SAA was rapidly incorporated into amyloid, acutely reducing circulating SAA concentrations by up to 90%. Prolonged modest SAA overexpression occasionally produced amyloidosis after long delays and primed most mice for explosive amyloidosis when SAA production subsequently increased. Endogenous priming and bulk amyloid deposition are thus separable events, each sensitive to plasma SAA concentration. Amyloid deposits slowly regressed with restoration of normal SAA production after doxycycline withdrawal. Reinduction of SAA overproduction revealed that, following amyloid regression, all mice were primed, especially for rapid glomerular amyloid deposition leading to renal failure, closely resembling the rapid onset of renal failure in clinical AA amyloidosis following acute exacerbation of inflammation. Clinical AA amyloidosis rarely involves the heart, but amyloidotic SAA transgenic mice consistently had minor cardiac amyloid deposits, enabling us to extend to the heart the demonstrable efficacy of our unique antibody therapy for elimination of visceral amyloid.     

Clinical strategies for amyloid A amyloidosis secondary to rheumatoid arthritis

Secondary amyloid A (AA) amyloidosis is an important complication of rheumatoid arthritis (RA) and has remarkable variation in frequency worldwide. It is a serious, potentially life-threatening disorder caused by deposition in organs of AA fibrils, which are derived from the circulatory, acute-phase-reactant, serum amyloid A protein (SAA). The SAA1.3 allele can serve not only as a risk factor for the association of AA amyloidosis but also as a poor prognostic factor in Japanese RA patients. Both the association of AA amyloidosis arising early in RA disease course and symptomatic variety and severity were found in amyloidotic patients carrying the SAA1.3 allele. Etanercept for patients with AA amyloidosis who carry the SAA1.3 allele showed the amelioration of rheumatoid inflammation, including marked reduction of SAA and improvement of renal function. In light of the SAA1.3 allele significance in Japanese RA patients, both a tight control by disease-modifying antirheumatic drugs and an early intervention of biologics for RA inflammation should be applied to suppress acute-phase response, thus preventing the association of AA amyloidosis. It is suggested that SAA plays not only an important role in the development of AA amyloidosis but also interacts with events closely involved in metabolic syndrome as a high- and low-grade inflammatory modulator, respectively.     

Alemtuzumab is safe and effective as immunosuppressive treatment for aplastic anaemia and single‐lineage marrow failure: a pilot study and a survey from the EBMT WPSAA

An alemtuzumab‐based experimental immunosuppressive treatment (IST) regimen was investigated in 35 patients with severe aplastic anaemia (SAA), pure red cell (PRCA) or pure white cell aplasia (PWCA). Alemtuzumab total dose was 73–103 mg s.c., followed by cyclosporine. No serious toxicity due to the regimen was observed. Adverse events were clinically irrelevant; infectious events were rare. The total response rate was 58%, 84% and 100% in SAA, PRCA and PWCA, respectively, with corresponding 6 months cumulative response probabilities of 84%, 84% and 100%. Subcutaneous alemtuzumab is a feasible and sufficiently safe IST regimen for patients suffering from immune‐mediated marrow failures.     

Quantification of HDL Proteins,Cardiac Events,and Mortality in Patients with Type 2 Diabetes on Hemodialysis

Background and objectives

Impairment of HDL function has been associated with cardiovascular events in patients with kidney failure. The protein composition of HDLs is altered in these patients, presumably compromising the cardioprotective effects of HDLs. This post hoc study assessed the relation of distinct HDL-bound proteins with cardiovascular outcomes in a dialysis population.

Design, setting, participants, & measurements

The concentrations of HDL-associated serum amyloid A (SAA) and surfactant protein B (SP-B) were measured in 1152 patients with type 2 diabetes mellitus on hemodialysis participating in The German Diabetes Dialysis Study who were randomly assigned to double-blind treatment of 20 mg atorvastatin daily or matching placebo. The association of SAA(HDL) and SP-B(HDL) with cardiovascular outcomes was assessed in multivariate regression models adjusted for known clinical risk factors.

Results

High concentrations of SAA(HDL) were significantly and positively associated with the risk of cardiac events (hazard ratio per 1 SD higher, 1.09; 95% confidence interval, 1.01 to 1.19). High concentrations of SP-B(HDL) were significantly associated with all-cause mortality (hazard ratio per 1 SD higher, 1.10; 95% confidence interval, 1.02 to 1.19). Adjustment for HDL cholesterol did not affect these associations.

Conclusions

In patients with diabetes on hemodialysis, SAA(HDL) and SP-B(HDL) were related to cardiac events and all-cause mortality, respectively, and they were independent of HDL cholesterol. These findings indicate that a remodeling of the HDL proteome was associated with a higher risk for cardiovascular events and mortality in patients with ESRD.     

Cellular events associated with the initial phase of AA amyloidogenesis: insights from a human monocyte model.

Reactive amyloidosis is a systemic protein deposition disease that develops in association with chronic inflammation. The deposits are composed of extracellular, fibrillar masses of amyloid A (AA) protein, an N-terminal fragment of the acute-phase serum protein serum amyloid A (SAA). The pathogenic conversion of SAA into amyloid has been studied in two human cell culture models, peritoneal cells and peripheral blood monocytes. Human monocyte cultures proved more robust than either mouse or human peritoneal cells at initiating amyloid formation in the absence of a preformed nidus such as amyloid-enhancing factor and particularly well suited for examination of individual cells undergoing amyloid formation. Amyloid-producing monocyte cultures were stained with Congo red and Alcian blue for detection of amyloid and glycosaminglycans, respectively; immunocytochemistry was performed to identify SAA/AA, CD68, CD14, lysosomal protein Lamp-1, and early endosomal protein EEA1. SAA interaction with monocytes was also visualized directly via fluorescence confocal microscopy. Amyloid was initially detected only in intracellular vesicles, but with time was seen extracellularly. Morphologic changes in lysosomes were noted during the early phase of amyloid formation, suggesting that exocytosis of fibrils may occur via lysosome-derived vesicles. Cultures engaged in amyloid formation remained metabolically active; no cytotoxic effects were observed. Mimicking in vivo phenomena, amyloid formation was accompanied by increased glycosaminoglycan content and C-terminal processing of SAA. The ability of human monocytes to endocytose and intracellularly transform SAA into amyloid via a mechanism that requires and maintains, rather than compromises, metabolic activity distinguishes them as a useful model for probing earliest events in the disease process.