原发性胆汁性肝硬化患者血清抗gp210抗体检测的意义

原发性胆汁性肝硬化(PBC)是一种以肝内小胆管进行性破坏为特征,并可在一定时期内进展为肝硬化的慢性疾病。抗线粒体抗体,尤其是抗M2抗体对于诊断PBC具有很高价值,但其与PBC病情程度及预后无关,且部分患者该抗体阴性。国内外已有文献报道抗核抗体特别是抗gp210抗体,与PBC的关系密切。归纳显示,抗gp210抗体诊断PBC特异性及敏感性均较高,且对于抗M2抗体阴性的PBC有更高检测价值,另外,其对于评估PBC预后及疾病发展模式有良好的预测价值。认为抗gp210抗体具有较高的检测意义及临床价值,值得广泛推广。     

AMA-M2抗体、gp210抗体和sp100抗体对原发性胆汁性胆管炎的诊断的价值探讨

[目的]探讨AMA-M2抗体、抗gp210和sp100抗体的检测对原发性胆汁性胆管炎(PBC)的诊断价值和意义。[方法]采取免疫印迹法检测62例PBC患者以及64例非PBC患者的抗线粒体抗体M2亚型(AMA-M2)、抗gp210及sp100抗体,分别计算这3种抗体的阳性率以及对PBC诊断的敏感性、特异性、阳性预测值、阴性预测值。[结果]62例PBC患者中,AMA-M2、抗gp210、sp100抗体的阳性率分别为75.8%、41.9%和19.4%,与非PBC组的阳性率比较差异有统计学意义;AMA-M2、抗gp210、sp100抗体诊断PBC的敏感性分别为:75.8%、41.9%和19.4%,特异性分别为:89.1%、95.3%和95.3%。AMA-M2阴性的PBC患者共15例,其中10例(66.7%)gp210抗体阳性,7例(46.7%)sp100抗体阳性。[结论]AMA-M2、抗gp210以及sp100抗体对PBC有高度的特异性。抗gp210以及sp100抗体对PBC的诊断尤其是AMA-M2阴性患者具有重要意义。     

抗gp210抗体在原发性胆汁性胆管炎中的产生机制与检测价值

原发性胆汁性胆管炎(PBC)是自身免疫性肝病之一，多数患者早期无明显临床表现，出现症状已至中晚期，尽早明确诊断及评估预后是非常必要的。抗gp210抗体对于诊断PBC及预测疾病进展有重要价值，检测该抗体可以优化PBC评分系统。本文总结评述了抗gp210抗体在PBC中的产生机制及检测的具体价值。     

表达gp210抗体的原发性胆汁性肝硬化患者临床特点分析

目的总结表达gp210抗体的原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)患者临床特点,为临床诊治提供循证医学依据。方法回顾性分析155例PBC患者,分为抗gp210阳性组63例、抗gp210阴性组92例,比较其症状、生化指标、免疫学指标、Mayo评分与Child评分、合并其他免疫性疾病情况及病理分期的特点差异。结果抗gp210阳性组和抗gp210阴性组在年龄、性别、临床表现、其他相关抗体阳性率、Mayo评分与Child评分及病理分期上的差异均无统计学意义(P0.05)。抗gp210阳性PBC患者Ig M、ALP均高于抗gp210阴性组(P0.05),而甲减发生率明显低于抗gp210阴性组(P0.05)。结论 gp210抗体对PBC的诊断有一定价值,可做抗线粒体抗体(anti-mitochondrial antibody,AMA)的有益补充,gp210与甲减是否有关有待进一步研究。     

流式荧光免疫法检测原发性胆汁性胆管炎自身抗体的价值与临床应用

目的对多重微球流式荧光免疫法(MBFFI)检测抗线粒体抗体(AMA) M2亚型、抗核孔膜蛋白抗体(gp210抗体)与抗核体蛋白抗体(sp100抗体)结果进行分析,并评估其对原发性胆汁性胆管炎(PBC)的诊断价值。方法选取2018年8月—2020年6月于青岛大学附属医院就诊并临床确诊的PBC患者340例(PBC组),其他疾病组143例,健康体检者117例。应用MBFFI与免疫印迹法(IBT)分别检测受试者血清中AMA-M2、gp210、sp100 3种自身抗体,用Kappa检验比较两种方法对同一种自身抗体检测结果的一致性;应用受试者工作特征曲线评估MBFFI检测3种抗体对PBC的诊断价值;阳性率的比较采用χ~2检验。结果PBC组中两种方法检测一致性最好的抗体为AMA-M2 (Kappa=0.874),gp210与sp100抗体的一致性较好(Kappa=0.713,Kappa=0.749)。MBFFI检测AMA-M2抗体的敏感度(72.06%)最高;联合检测gp210与sp100两种抗体的敏感度(44.71%)高于单项抗体,联合检测AMA-M2、gp210与sp100 3种抗体的敏感度(82.65%)高于单项抗体。3种抗体联合检测诊断PBC的受试者工作特征曲线下面积最大(0.907 0)。结论 MBFFI检测PBC自身抗体与IBT检测结果一致性较好。MBFFI联合检测AMA-M2、gp210和sp100抗体诊断PBC的敏感度更高,诊断价值更大。     

抗gp210抗体阳性原发性胆汁性胆管炎患者临床特点研究

目的:大样本分析抗糖蛋白210抗体（抗gp210抗体）阳性原发性胆汁性胆管炎（PBC）患者的临床特征及其对预后的影响。方法:回顾性研究首都医科大学附属北京佑安医院2010-2019年PBC患者931例。根据抗gp210抗体检测情况分为：抗gp210抗体阳性组（阳性组）318例和抗gp210抗体阴性组（阴性组）613例,...     

自身抗体检测在PBC和AIH诊断中的临床价值

目的探讨检测多种自身抗体在原发性胆汁性肝硬化（PBC）和自身免疫性肝炎（AIH）诊断中的临床价值。方法采用间接免疫荧光法检测抗核抗体（ANA）、采用免疫印迹法检测AMA—M2、抗Sp100、抗gp210、抗肝肾微粒体-1（LKM—I）、抗肝特异性胞质1型（LC-1）、抗可溶性肝抗原／肝胰抗原（抗SLA／LP）和抗Ro-52。结果在30例PBC患者,AMA—M2、抗Sp100、抗gp210、抗LKM-1、抗LC-1、抗SLA、抗R0—52和ANA阳性率分别为80．0％、13．3％、46．7％、0．0％、10．0％、6．7％、56．7％和66．7％,而在30例AIH患者,其阳件率分别为20．0％、10．0％、6．7％、10．0％、3．3％、10．0％、60％和90．0％;在PBC患者未检测出抗LKM—1,而其在A1H患者为11．11％。结论AMA—M2和抗gp210对PBC有较高的诊断价值,而LKM—1对AIH具有较高的诊断价值。     

抗gp210抗sp100抗体与原发性胆汁性肝硬化活动性的相关性

目的 评估原发性胆汁性肝硬化(PBC)患者血清中抗gp210和抗sp100抗体与PBC活动性的关系.方法 采集72例PBC患者的静脉血,以酶联免疫吸附试验(ELISA)检测抗gp210、抗sp100的水平,分析患者的临床资料.结果 抗gp210阳性患者白蛋白水平较阴性组降低,Mayo危险评分较后者升高,差异均有统计学意义(分别为P＜0.01和P＜0.05).随着疾病好转,抗gp210抗体多呈下降趋势.抗sp100阳性组与阴性组在血清生化指标、Mayo危险评分方面差异均无统计学意义.结论 抗gp210阳性患者病情较重,需加强随访,积极治疗.     

原发性胆汁性肝硬化与抗gp210抗sp100抗体相关性的研究

目的 检测原发性胆汁性肝硬化(PBC)患者血清中抗gp210、抗sp100的抗体水平,比较上述抗体检测对PBC诊断的敏感性和特异性,明确其在PBC诊治中的意义.方法 采集61例PBC、28例干燥综合征(SS)、11例PBC合并SS以及22例乙型病毒性肝炎患者的新鲜静脉血离心取血清标本,以酶联免疫吸附试验(EUSA)检测抗gp210、抗sp100的水平,分析患者的临床资料,比较不同疾病之间此3种抗体水平.结果 PBC和PBC合并SS患者抗gp210阳性率分别为31.1%和45.5%,与SS组和病毒性肝炎组比较,差异有统计学意义(P＜0.01).PBC组和PBC合并SS组抗gp210阳性率差异无统计学意义.PBC和PBC合并SS患者抗sp100阳性率分别为14.8%、18.2%,明显高于病毒性肝炎组(P均＜0.01).SS组阳性率3.3%,PBC组、SS组和PBC合并SS组之间抗sp100阳性率差异无统计学意义.结论 抗gp210、抗sp100抗体对PBC诊断的敏感性和特异性分别为31.1%和100.0%、14.8%和98.0%,可协助诊断PBC.     

多种自身抗体联合检测在原发性胆汁性肝硬化中的诊断价值

目的探讨3种自身抗体(抗-线粒体M2亚型、抗-gp210、抗-Sp100)的联合检测在原发性胆汁性肝硬化中的诊断价值。方法选择2000例隐匿性肝炎患者,根据疾病诊断分为原发性胆汁性肝硬化(PBC)组129例(6.45%)、自身免疫性肝炎(AIH)组205例(10.25%)、AIH-PBC重叠综合征组15例(0.75%)、脂肪肝组514例(25.70%)、药物性肝炎组379例(18.96%)、其他不明原因肝炎组758例(37.90%)。选择同期健康者15例作为对照组。采用ELISA法检测2000例隐匿性肝炎患者血清中抗-线粒体M2亚型(AMA-M2)、抗-核包膜蛋白gp210(anti-gp210)、抗-可溶性酸性磷酸化核蛋白Sp100(anti-Sp100),结合自身免疫性肝病、脂肪性肝病、药物性肝病等疾病的诊断标准进行筛查分析。结果 PBC组AMA-M2、抗-gp210、抗-Sp100阳性率分别为97.67%(126/129)、41.86%(54/129)、27.91%(36/129),抗-gp210、抗-Sp100两者同时出现的阳性率为9.30%(12/129)。12例抗-gp210和抗Sp100抗体阳性的不明原因肝炎患者经肝组织活检后有3例诊断为PBC。PBC组有62.80%(81/129)的AMA-M2抗体滴度水平在1︰800以上,有13.95%(18/129)的AMA-M2抗体滴度水平为1︰25～100,有9.30%(12/129)的AMA-M2抗体滴度水平为1︰100～200。结论 MA-M2阳性仍是诊断PBC的主要诊断指标,AMA-M2、抗-gp210、抗-Sp100的联合检测对PBC的诊断具有较高的应用价值,对筛查其他自身免疫肝病有较好的辅助作用。     

Autoantibodies against a 210kDa glycoprotein of the nuclear pore complex as a prognostic marker in patients with primary biliary cirrhosis

It has been reported that the presence of anti-nuclear antibody against a 210kDa glycoprotein of nuclear pore complex (anti-gp210) is highly speci?c for primary biliary cirrhosis (PBC). The aim of the present study was to investigate the signi?cance of anti-gp210, especially as a prognostic marker. The presence of anti-gp210 was ascertained in 113 patients with PBC and 162 controls by indirect immuno?uorescence assay using HepG2 cells and immunoblotting analysis using nuclear extracts from HeLa cells. Anti-gp210 was detected in 25 of the 113 (22.1%) patients. None of the 162 controls was positive for anti-gp210. The appearance and titre of anti-gp210 in the patients with PBC did not vary from the time of diagnosis and through their clinical course. Anti-mitochondrial antibodies (AMA), including antibodies against pyruvate dehydrogenase complex, branched chain α-ketoacid dehydrogenase complex and α-ketoglutarate dehydrogenase complex, were not detected by enzyme-linked immunosorbent assay in ?ve of the 113 (4.4%) patients with PBC. However, anti-gp210 alone was positive in one of these ?ve patients. The difference in prognosis was statistically signi?cant; patients with PBC positive for anti-gp210 died from hepatic failure more frequently than those who were negative (P < 0.01), although there were no statistically signi?cant differences in the frequency of jaundice and the histological stage at the time of diagnosis between the two groups. We suggest that the presence of anti-gp210 is one of the independent prognostic markers able to predict, at the time of diagnosis, a poor outcome in patients with PBC.     

Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis

BACKGROUND/AIMS: The presence of antibodies to the 210-kDa glycoprotein of the nuclear pore complex (gp210) is highly indicative of primary biliary cirrhosis (PBC). However, the significance of anti-gp210 antibody titers for monitoring PBC remains unresolved. METHODS: We used an ELISA with a gp210 C-terminal peptide as an antigen to assess serum antibody titers in 71 patients with PBC. RESULTS: Patients were classified into three groups: Group A in whom anti-gp210 titers were sustained at a high level, Group B in whom anti-gp210 status changed from positive to negative under ursodeoxycholic acid (UDCA) therapy, Group C in whom anti-gp210 antibodies were negative at the time of diagnosis. The rate of progression to end-stage hepatic failure was significantly higher in group A (60%) as compared to groups B (0%) and C (4.2%). The sustained antibody response to gp210 was closely associated with the severity of interface hepatitis. The significance of anti-gp210 antibody was confirmed by National Hospital Organization Study Group for Liver Disease in Japan. CONCLUSIONS: The serial quantitation of serum anti-gp210-C-terminal peptide antibodies is useful for monitoring the effect of UDCA and for the early identification of patients at high risk for end-stage hepatic failure.     

The prognostic value of antibodies to gp210 among patients with primary biliary cholangitis in Northeast China

BackgroundWhether the anti-gp210 antibody can be used as a biomarker in patients with primary biliary cholangitis (PBC) remains controversial.AimsWe aimed to investigate the association between anti-gp210 antibodies and prognosis in ursodeoxycholic acid (UDCA)-treated PBC patients.MethodsWe conducted a retrospective cohort study of 180 UDCA-treated PBC patients to assess the prognostic value of anti-gp210 antibodies using the Kaplan–Meier method and Cox proportional hazard regression analysis.ResultsOf the patients included in our analysis, 50 (27.8%) were anti-gp210 positive, and 130 (72.2%) were anti-gp210 negative. The incidence of liver-related death or transplantation was more common in the anti-gp210 + group (22.0 vs. 9.2%, P=0.022). The five-year transplant-free survival rates of anti-gp210-positive patients vs. anti-gp210-negative patients were 77.0% and 90.3%, respectively. We found that the probability of transplant-free survival was significantly lower in the anti-gp210-positive patients than in the anti-gp210-negative patients (log-rank P=0.004). After adjusting for potential confounders using multivariable Cox regression model, positivity for anti-gp210 antibody (hazard ratio: 4.619, 95% confidence interval: 1.895–11.261, P=0.001) was found to be independently associated with an increase in liver-related mortality or transplantation.ConclusionIn this cohort of UDCA-treated PBC patients, positivity for anti-gp210 antibody was independently associated with a higher risk of liver-related death or transplantation.     

Nuclear envelope protein autoantigens in primary biliary cirrhosis

Antinuclear antibodies are detectable in approximately 50% of subjects with primary biliary cirrhosis (PBC). Most clinical laboratories use indirect immunofluorescence microscopy to detect antinuclear antibodies and two labeling patterns that predominate in PBC are nuclear rim and multiple nuclear dots. Antibodies giving these patterns most often recognize nuclear envelope protein gp210 and nuclear body protein sp100, respectively. Fewer subjects with PBC have autoantibodies giving nuclear rim labeling that recognize nucleoporin p62 and LBR. Gp210 is an integral protein localized to the nuclear pore membranes. Approximately 25% of subjects with PBC have detectable serum anti-gp210 antibodies. The vast majority of anti-gp210 antibodies from patients with PBC recognize a stretch of only 15 amino acids in the carboxyl-terminal tail that faces the nuclear pore complex. Enzyme-linked immunosorbent assays using either recombinant protein expressed in bacteria or chemically synthesized polypeptides have been established to reliably detect these autoantibodies. Although initial studies did not find a correlation between the presence of anti-gp210 antibodies and prognosis in PBC, recent data suggest that the presence of antinuclear envelope protein antibodies correlate with an unfavorable disease course and more rapid progression.     

Antimitochondrial antibodies and other antibodies in primary biliary cirrhosis: diagnostic and prognostic value

Antimitochondrial antibodies (AMA) are the serologic cornerstone in the diagnosis of primary biliary cirrhosis (PBC), even if they are not detectable in a proportion of patients, notwithstanding the most sensitive and sophisticated technologies used. To fill in the serologic gap in AMA-negative PBC, there is sound evidence to consider antinuclear antibody (ANA) patterns, such as anti-multiple nuclear dots and anti-membranous/rim-like, as PBC-specific surrogate hallmarks of the disease, and their detection can be considered virtually diagnostic. Furthermore, particular ANA specificities, such as anti-gp210, anti-p62, anticentromere antibodies, and anti-dsDNA, may provide additional diagnostic and prognostic information.     

Anti-gp210 and anti-Sp100 antibodies in primary biliary cholangitis

Background and study aimsTo determine the sensitivity and specificity of anti-gp210 and anti-Sp100 autoantibodies in primary biliary cholangitis (PBC)Patients and MethodsSera of 106 PBC patients with positive anti-mitochondrial antibodies and 58 healthy blood donors were analyzed. A line immunoassay was used to evaluate the reactivity of anti-gp210 and anti-Sp100 antibodies.ResultsThe frequency of anti-gp210 and anti-Sp100 autoantibodies was 29.2% and 28.3%, respectively. Eight patients had both anti-gp210 and anti-Sp100 antibodies. Of 106 patients, 23 (21.7%) had anti-gp210 antibody, although not anti-Sp100 antibody, and 22 (20.7%) had anti-Sp100, although not anti-gp210 antibodies. Their combination increased the frequency of anti-gp210 and anti-Sp100 antibodies from 29.2% to 50% (P = 0.002) and 28.3% to 50% (P = 0.0012), respectively. In the control group, two subjects had anti-gp210 antibody and none had anti-Sp100 antibody. Thus, the specificity of anti-gp210 and anti-Sp100 antibodies was 96.5% and 100%, respectively. The positive predictive value (PPV) of anti-gp210 antibody was 94%; its negative predictive value (NPV) was 42.7%. The PPV and NPV of anti-Sp100 antibody were 100% and 43.3%, respectively.ConclusionIt is important to combine anti-gp210 and anti-Sp100 antibodies in the immunological exploration of PBC.     

A male patient who developed late-onset primary biliary cirrhosis presenting with antinuclear envelope antibodies

 An 81-year-old man who had previously shown high levels of alkaline phosphatase (ALP), γ-glutamyltransferase (GTP), and total bilirubin presented with acute liver damage. He was positive for serum anti-gp210 and anti-p62 antibodies, but negative for serum antimitochondrial antibody. A liver biopsy revealed massive interstitial fibrosis and pseudolobulus, which were compatible with a diagnosis of primary biliary cirrhosis (PBC) at Scheuer's stage 4. He was given ursodeoxycolic acid at 600 mg/day. However, his condition deteriorated, and he eventually died of hepatic insufficiency in a state of malnutrition. We hypothesize that the presence of anti-gp210 and anti-p62 complex protein antibodies, rather than that of antimitochondrial antibodies, was correlated with the progression of PBC in this particular case. Received: December 18, 2000 / Accepted: December 26, 2001 Acknowledgments We thank Dr. Eng M. Tan of the W.M. Keck Foundation, Scripps Research Institute, LaJolla, California, USA, for the determination of antilamina-associated polypeptide (LAP)-2 antibodies in the SS patient included as a control in this study. We also thank Dr. P.A. Berg of Tubingen University for the determination of anti-M4 and anti-M8 antibodies. Correspondence to: K. Miyachi