IgG4相关肝胆疾病诊疗进展

IgG4相关性疾病是一类以淋巴浆细胞性炎症为主,伴血清和组织中IgG4增多并累及多器官或组织的慢性进行性全身性炎性疾病,累及肝胆胰腺系统时称之为IgG4相关肝胆疾病。简述了IgG4相关自身免疫性胰腺炎、IgG4相关硬化性胆管炎、IgG4相关自身免疫性肝炎的临床表现和实验室检查等方面。准确识别IgG4相关肝胆疾病的各个实验室结果,并正确诊断此类疾病,有助于避免不必要的手术和错误的治疗。

一种简便可较大量提取血清IgG的方法

用辛酸沉淀法结合应用少量阴离子交换剂纯化了四种动物抗血清及正常猪、羊血清的IgG。本法与硫酸铵法、亲和层析法纯化的IgG均呈现相同的电泳纯条带。本法简便、经济、回收率好,可较大量提取血清IgG。提纯过程保存抗体原有生物活性。

Clinical Study on the Treatment of Male Immune Infertility with Sheng Jing Zhong Zi Tang

Using Sheng Jing Zhong Zi Tang (生精种子汤Decoction for Promoting Generation of Vital Energy), we have in recent years treated 90 cases of masculine infertility and obtained quite good therapeutic effects. A report follows.

Advances in TCM Symptomatology of Rheumatoid Arthritis

In view of the rich experiences and new advances in TCM treatment of rheumatoid arthritis, it is very promising to find a further breakthough in the field of traditional Chinese medicine (TCM). Treating the disease by means of differentiation of symptoms and signs is a distinctive feature of TCM, however the difficult and also the major point would be the research of mechanism of its symptomatology. The following is a summary of the advances in the study of symptomatology, especially its epidemiology, the role of immune system and blood rheology made since 1987 when the ARA criteria1 was published.……

Diagnostic criteria for autoimmune hepatitis in children: A challenge for pediatric hepatologists

Autoimmune hepatitis (AIH) is a progressive inflammatory liver disorder that is rare in children and adolescents. AIH has a broad clinical spectrum and a quick response to treatment with corticosteroids and immunosuppressive medication. The available diagnosis criteria have limitations and should be evaluated in pediatric populations. Recently, some studies reported that the 2008 simplified diagnostic criteria for AIH could be used in children with high sensibility and specificity. In addition, the authors reported that globulin and immunoglobulin G levels can be used interchangeably for diagnostic purposes. They also demonstrated that the 2008 simplified criteria fail in identifying patients with fulminant hepatic failure. Here, we discuss the limitations of the use of these criteria in pediatric patients and the requirement of more studies to improve the diagnosis of AIH in children.

Newly developed autoimmune cholangitis without relapse of autoimmune pancreatitis after discontinuing prednisolone

A 57-year-old man presented with a 2-wk history of painless jaundice and weight Iossl He had a large ill- defined enhancing mass-like lesion in the uncinate pro- cess of the pancreas with stricture of the distal common bile duct. Aspiration cytology of the pancreatic mass demonstrated inflammatory cells without evidence of malignancy. Total serum immunoglobulin G level was slightly elevated, but IgG4 level was normal. After the 2-wk 40 mg prednisolone trial, the patient＇s symptoms and bilirubin level improved significantly. A follow-up computed tomography （CT） scan showed a dramatic resolution of the pancreatic lesion. A low dose steroid was continued. After six months he self-discontinued prednisolone for 3 wk, and was presented with jaundice again. ACT scan showed newly developed intrahepatic biliary dilatation and marked concentric wall thickening of the common hepatic duct and the proximal common bile duct without pancreatic aggravation. The patient＇ s IgG4 level was elevated to 2.51 g/L. Prednisolone was started again, after which his serum bilirubin level became normal and the thickening of the bile duct was resolved. This case suggests that autoimmune pancre- atitis can progress to other organs that are not involved at the initial diagnosis, even with sustained pancreatic remission.

Specific serum immunoglobulin G to H pylori and CagA in healthy children and adults(south-east of Iran)

AIM. To evaluate the serologic IgG response to Hpylori and CagA across age groups and in healthy children and adults.METHODS： Totally, 386 children aged 1-15 years and 200 adults aged 20-60 years, were enrolled to study. The serum samples of participant were tested for presence of antJ-Hpylori and anti-CagA IgG by using ELISA method.RESULTS： The seroprevalence of Hpylori in adults was significantly higher than that observed in children （67.5% vs 46.6%; P 〈 0.000003）. In children, the seropositivity rate in males （51.9%） was significantly （P 〈 0.05） higher than that observed in females （41.7%）. The prevalence of serum anti-CagA antibody was 72.8% and 67.4% in infected children and adults, respectively. The mean titer of serum anti-CagA antibodies was significantly higher among children in comparison to adults （64.1 Uarb/mL 30.7; P 〈 0.03）. In infected children and adults the prevalence of serum anti-CagA antibody was higher in males compared to females （78.4% vs 66.3%; P = 0.07 and 75.6% vs 54.71%; P 〈 0.04, respectively）. The age-specific prevalence of anti-H py/or/and anti-CagA antibody （in infected subjects） was 37.6% and 59.57% at age 1-5 years, 46.9% and 75% at age 6-10 years, 54.9% and 79.45% at age 11-15, 59.01% and 83.33% at age 20-30 years, 66.6% and 60.52% at age 31-40 years, 73.46% and 63.88% at age 41-50 years and 75.75% and 60% at age 51-60 years with mean titer of anti-CagA antibody of 75.94, 63.32, 57.11, 52.06, 23.62, 21.52 and 21.80 Uarb/mL, respectively. There was significant difference between mean serum anti-CagA antibody in age subgroups （P 〈 0.001）.CONCLUSION： These results showed that anti-Hpylori and anti-CagA antibodies were common in the children and adults. The Hpylori-specific antibodies influenced by age and sex of subjects. Moreover, it seems that males are more susceptible to infection with CagA^＋ strains compared to females. The seroprevalence of anti-CagA antibody was increased with age, up to 30 years and then decreased. It was also found that the magnitude of the IgG response to CagA decreased with advanced age.

Evaluation of Coagglutination Test Kit for Red Sea Bream Iridovirus

Coagulation test, in principle, is an immunodiagnostics technique, in which immunoglobuline G of antibody is bound to protein A from Staphylococcus aureus. The aim of study is to develop a rapid test kit for detecting iridovirus infection in fish. Method was summarized as follows： （1） vaccine of iridovirus was injected to rabbit four times with a dosage as 0.5 mL, 1 mL, 2mL, 3 mL each week. Serum was collected at the fifth week as a coagglutination test kit; （2） through the positif polymerase chain reaction （PCR） test, the kidney and spleen sample infected with iridovirus are homogenized by using the phosphate buffered saline （PBS） solution of pH 7.2 with ratio 1：2 （WN）; （3） the supernatant material is collected after centrifugation at 8,000 rpm for 15 min; （4） filtrate/supernatant from sample was dropped on a slide an added with coagglutination test kit with the same volume （l：l）; （5） the agglutination observation is done after the 30, 60 and 90 min incubate at room temperature. The coagglutination test gave positive result in 25% of the test samples.

MODIFICATION OF TRYPTOPHAN RESIDUES OF IgGRF AND ITS EFFECT ON THE ADSORPTION CAPACITY

Tryptophan residues of IgGRF from rheumatoid arthritis patient were modified with N-Bromosuccinimide (NBS) and the product of modification was characterized by UV-spectrum、Fluorescence emission spectrum and CD-spectrum. The corresponding adsorption capacity of immobilized ssDNA immunoadsorbent for IgGRF was enhanced from 46% to 86%, This result indicates the tryptophan residue is essential for the interaction between ssDNA and IgGRF .and ionic-bonding plays an important role in adsorption.

丝虫特异IgG4酶联免疫吸附测定试验检测试剂盒应用价值的研究

目的探讨丝虫特异Ig G4酶联免疫吸附测定试验(ELISA)检测试剂盒检测丝虫病患者血清和滤纸血中特异Ig G4亚类抗体的敏感度和特异度并评价其应用价值。方法应用丝虫特异Ig G4 ELISA检测试剂盒,检测微丝蚴阳性患者血清或滤纸血、其他蠕虫患者血清、晚期丝虫病患者滤纸血、原微丝蚴血症转阴者滤纸血和基本消除丝虫病后出生儿童滤纸血以及消除丝虫病后不同时间居民血清或滤纸血样本。采用两相关样本的非参数检验,分析血清与滤纸血检测相同稀释度下的Ig G4的A值差异。结果检测86例微丝蚴阳性患者血清,显示丝虫特异Ig G4阳性81例,阳性符合率94.19%。检测97份其他蠕虫患者血清、58份阴性冻存血清和100份正常健康人对照血清,显示丝虫特异Ig G4全部阴性,阴性符合率100%。4例现症微丝蚴血症患者,血清和滤纸血丝虫特异Ig G4全部阳性,血清阳性吸光度(A)值均高于同一患者滤纸血样本A值,但差异无统计学意义(Z=-1.826,P>0.05)。检测48例晚期丝虫病患者滤纸血、76例原微丝蚴血症转阴者滤纸血、312例基本消除丝虫病地区1983年后出生儿童滤纸血,显示丝虫特异Ig G4全部阴性。检测原丝虫病高中度流行地区消除丝虫病后的枣庄、泰安和济宁地市居民滤纸血和血清样本分别为2 744份、2 243份和800份,显示丝虫特异Ig G4全部阴性。结论丝虫特异Ig G4酶联免疫吸附测定试验的检测试剂盒敏感度高、特异度强、操作简便快捷,特别适用于丝虫病诊断和消除丝虫病地区的疾病监测。

Update on autoimmune hepatitis

Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown etiology that occurs in children and adults of all ages. Characteristics are its autoimmune features,hyperglobulinemia (IgG),and the presence of circulating autoantibodies,as well as a response to immunosuppressant drugs. Current treatment consists of prednisone and azathioprine and in most patients this disease has become very treatable. Over the past 2 years,a couple of new insights into the genetic aspects,clinical course and treatment of AIH have been reported,which will be the focus of this review. In particular,we concentrate on genome-wide microsatellite analysis,a novel mouse model of AIH,the evaluation of a large AIH cohort for overlap syndromes,suggested novel criteria for the diagnosis of AIH,and the latest studies on treatment of AIH with budenoside and mycophenolate mofetil.

CLINICAL OBSERVATION ON THERAPEUTIC EFFECT OF ACUPUNCTURE AT ZUSANLI FOR LEUKOPENIA

In recent years, leukopenia is clinically very common. The leukopenic patient is significantly low in immunocompetence and is likely to suffer from various kinds of infections. Zusanli (St 36), an

眼眶IgG4相关疾病的临床病理学特点及其鉴别诊断

目的 探讨眼眶IgG4相关疾病（IgG4-ROD）的临床及组织病理学特点及其与眼眶非IgG4相关疾病（Non-IgG4-ROD）的鉴别诊断.方法 回顾性系列病例研究.收集2008年11月至2014年8月四川大学华西医院病理科的43例患者的临床资料.分析其临床表现、实验室检查、影像学结果、治疗情况及组织病理学特点.根据2014年IgG4-ROD的诊断标准和相关文献报道,本组研究病例分为2组：IgG4-ROD（18例,23份眼眶标本）和Non-IgG4-ROD（25例,31份眼眶标本）.男女构成、淋巴滤泡的形成、导管及血管周围的纤维化、眼眶的病变范围采用Pearson x2检验,年龄、免疫组织化学IgG4＋/HPF浆细胞数、IgG＋/HPF浆细胞数、IgG4＋/IgG＋浆细胞比值采用两样本比较的t检验,病变累及的结构组织及形态学指标嗜酸性粒细胞和淋巴细胞和浆细胞的浸润采用配对设计的符号秩和检验.结果 两组病例在以下参数中的差异具有统计学意义：IgG4-ROD组每个高倍视野IgG4＋浆细胞数（＞40个/HPF）（t=12.17,P＜0.01）,IgG＋浆细胞数（＞100个/HPF） （t=2.91,P＜0.01）,IgG4＋/IgG＋浆细胞比值（≥40％）（t=16.98,P＜0.01）,淋巴细胞和浆细胞的浸润（F=3.62,P=0.03）,导管周围的纤维化（F=4.71,P=0.03）,眼眶病变范围（t=1.11,P=0.01）.但是在平均年龄（t=1.17,P=0.28）,男女构成（t=1.09,P=0.58）的差异无统计学意义.IgG4-ROD需要与眼眶非特异性的炎性病变、淋巴瘤等鉴别.结论 眼眶IgG4相关疾病主要发生在中老年男性,双侧眼眶无痛性肿胀为眼部常见症状,病变组织特点为大量IgG4＋浆细胞浸润,并可以累及眼眶多种结构组织,以泪腺为主,但未见典型的闭塞性静脉炎改变.充分结合临床表现、影像学发现、实验室检查和组织病理学改变有助于与Non-IgG4-ROD及其他疾病进行鉴别诊断.

Highly Sensitive Protein Sensor Based on Thermally-Reduced Graphene Oxide Field-Effect Transistor

We report the fabrication of a highly sensitive field-effect transistor （FET） biosensor using thermally-reduced graphene oxide （TRGO） sheets functionalized with gold nanoparticle （NP）-antibody conjugates. Probe antibody was labeled on the surface of TRGO sheets through Au NPs and electrical detection of protein binding （Immunoglobulin G/IgG and anti-lmmunoglobulin G/anti-lgG） was accomplished by FET and direct current （dc） measurements. The protein binding events induced significant changes in the resistance of the TRGO sheet, which is referred to as the sensor response. The dependence of the sensor response on the TRGO base resistance in the sensor and the antibody areal density on the TRGO sheet was systematically studied, from which a correlation of the sensor response with sensor parameters was found： the sensor response was more significant with larger TRGO base resistance and higher antibody areal density. The detection limit of the novel biosensor was around the 0.2 ng/rnL level, which is among the best of,＇eported carbon nanomaterial-based protein sensors and can be further optimized by tuning the sensor structure.

Label-free and real-time detection of antigen-antibody interactions by Oblique-incidence Reflectivity Difference(OIRD) method

We label-free and real-time detected three interaction processes of antigen-antibodies,Human Immunoglobulin G(IgG),Rabbit IgG,and Mouse IgG as the targets,and Goat Anti-human IgG,Goat Anti-rabbit IgG,and Goat Anti-mouse IgG as the probe,by the Oblique-incidence Reflectivity Difference(OIRD) method.The interaction dynamic curves of the OIRD signal,corresponding to the interaction processes of antigen-antibodies,are generated.The reaction times from beginning to equilibrium state are about 1800,900,and 1200 s for Human IgG,Rabbit IgG,and Mouse IgG,respectively.The experimental results demonstrate that the OIRD method not only can distinguish biomolecular interactions,but also can be used in real-time detection of interactions and dynamic processes of biomolecules.

Biological indicators of sub-optimal health status

OBJECTIVE:To investigate biological indicators of sub-optimal health status and provide means of objective assessment of sub-optimal health status.METHODS:We set the unified standards for diagnosing a SHS.We tested various laboratory indicators in 407 cases that we selected randomly from2807 subjects and collected 15 mL of fasting venous blood from each case.We measured serum immunoglobulin A(IgA)and immunoglobulin G(IgG)concentrations,serum beta endorphins(β-EP),cortisol(C),testosterone(T),plasma adrenocorticotropic hormone(ACTH)and serum T lymphocyte subsets CD3+and CD4+.RESULTS:Mean serum testosterone concentrations and their ratio to cortisol(C)concentrations weresignificantly higher in the healthy group than in those with sub-optimal health status(P<0.01).Mean serum CD3+concentrations were significantly higher in those with sub-optimal health status than in the healthy group(P<0.05).CONCLUSION:Decreased serum testosterone/cortisol ratio may be an objective indication of sub-optimal health status.Changes in neuroendocrine and immunological indicators may explain some of the symptoms,including malaise and poor work performance,attributable to persistent or relapsing fatigue in subjects with sub-optimal health status.

The study of 3-dimensional structures of IgG with atomic force microscopy

Objective ： To detect 3-dimensional images of anti-N-methyl-D-aspartate receptor Nrl （ NMDAr1 ） polycolonal lgG affixed on mica in physiological environment. Methods： The images and data were obtained from a contact mode and commercial Si3N4 probed tip by using atomic force microscope （ AFM ）. Results： The anti-NMDArl polycolonal IgG has a characteristic structure described as an ellipse spherical shape of 136.4 A × 62.8 A × 26.1 A. On the section of theellipse edge there were two peaks about 13nm in width. Conclusions ： Using AFM to investigate biomacromolecule can make us deeply understand the structure of IgG, which will instruct us to detect the membrane receptor protein as a labelling agent.

Ultrasensitive label-free electrochemiluminescence immunosensor based on N-(4-aminobutyl)-N-ethylisoluminol-functionalized graphene composite

The electrochemiluminescence(ECL) behavior of N-(4-aminobutyl)-N-ethylisoluminol(ABEI)-functionalized graphene composite(ABEI-GC) modified on an indium tin oxide(ITO) electrode was studied. ABEI-GC exhibited excellent ECL activity. On this basis, a label-free ECL immunosensor was developed for the sensitive detection of human immunoglobulin G(h Ig G) by using ABEI-GC as the ECL nano-interface via a layer-by-layer assembly technique. ABEI-GC was first assembled onto an ITO electrode. Positively charged chitosan was then electrostatically adsorbed to the modified electrode. Finally, negatively charged antibody-coated gold nanoparticles were attached to the surface to form the ECL immunosensor. In the presence of h Ig G, h Ig G was captured by its antibody. In addition, an ECL signal was detected in the presence of H2O2 when a double potential was applied. The ECL immunosensor for the determination of h Ig G showed a linear range of 1.0×10-13–1.0×10-8 g/mL with a detection limit of 5.0×10-14 g/m L. This immunosensor has high sensitivity, wide linearity and good reproducibility. The superior sensitivity of the proposed ECL immunoassay mainly derives from the incorporation of ABEI-GC, which not only improves the ECL intensity, response speed, and stability, but also provides a large specific surface for high levels of protein loading. This work reveals that ABEI-GC is good nano-interface for the construction of ECL biosensors. Our strategy is promising for protein detection and may open up a new avenue for ultrasensitive label-free immunoassays.

Surface modification of hydrophobic NaYF_4:Yb,Er upconversion nanophosphors and their applications for immunoassay

β-NaYFa：Yb,Er upconversion nanophosphor （UCNP） is known as one of the most efficient NIR-to-visible upconversion mate- dais, which shows great potential in bioanalytical chemistry and bioimaging. However, its applications are greatly limited due to its low water dispersibility and thus poor biocompatibility. In this paper, poly（acrylic acid） （PAA）-based ligand exchange strategies are carded out to modify oleic acid-capped hydrophobic β-NaYF4：Yb,Er UCNPs into hydrophilic ones. After efficient surface modification, the presence of free carboxylic acid groups on the surfaces of UCNPs results in high solubility in water, and also allows further conjugation with NH2-containing biomolecules. Facilitated by the covalent linkage between the -COOH groups on UCNPs surfaces and -NHz groups in antigen/antibody, a sensitive immunosensor is constructed by using PAA-functionalized β-NaYFa：Yb,Er UCNPs as biolabels. Through monitoring the upconversion fluorescence intensity or fluorescent imaging of the final immunocomplexes, high sensitivity is achieved for the proposed immunoassay and as low as 0.1 ng/mL goat anti-human immunoglobulin G （IgG） can be detected, which suggests that PAA-modified UCNPs may serve as an ideal candidate for use as bioanalysis and bioimaging probes.