原发性胆汁性肝硬化自身抗体的研究进展

原发性胆汁性肝硬化（pfimary biliary cirrhosis，PBC）是一种原因不明的慢性胆汁淤积性自身免疫性肝病，其确切的发病机制尚未明确，可能涉及遗传、免疫及环境因素。其中体液免疫可能扮演了重要角色，引起了临床上的高度关注，血清中高滴度的抗线粒体抗体（antimitochondrial antibodies，AMA）已成为PBC诊断的重要指标。本文旨在探讨该领域的最新进展，以期加深对其爱病机制的理解，为临床诊治提供进一步的依据。     

原发性胆汁性肝硬化研究进展

原发性胆汁性肝硬化 (primarybiliarycirrhosis,PBC)是一种慢性肝内胆汁淤积性疾病 ,国外报道PBC的发病率为 2～ 2 4 / 10万 ,年发病率为 0 .4～ 3.0 / 10万 ,且呈逐年增长趋势。PBC早期症状轻微 ,临床表现不典型 ,极易误诊为病毒性肝炎 ,而使病情迁延发展 ,造成严重后果。一、PBC的临床表现(一 )PBC的临床表现及分期PBC是由自身免疫介导的肝内损伤 ,可形成进行性炎性瘢痕 ,最终导致肝功能衰竭。PBC患者最初的临床表现为嗜睡和皮肤瘙痒 ,后期出现黄疸 ,并伴有肝功能衰竭。根据PBC病程进展自然经过 ,一般将其分为四个时期 :1.肝功…     

原发性胆汁性肝硬化患者自身抗体检测及其临床意义

目的 探讨血清自身抗体对原发性胆汁性肝硬化(PBC)的诊断及其临床意义.方法 对PBC患者采用间接免疫荧光、免疫印迹法检测抗核抗体(ANA)、抗平滑肌抗体(SMA)、抗线粒体抗体(AMA),并对AMAM2亚型及其抗可溶性肝抗原/肝胰抗原(SLA/Le)、抗肝肾微粒体Ⅰ型(LKM-1)和抗肝特异性胞浆Ⅰ型抗体(LC-1)等肝脏疾病相关的自身抗体进行检测.结果 PBC患者自身抗体以AMA和AMAM2亚型为主.其阳性率分别为96.5%和93.1%.患者的抗体滴度均大于1:100,其中有8例出现ANA和SMA,1例出现AMA和SLA/LP同时阳性,表现与Ⅰ型和Ⅲ型自身免疫性肝炎重叠,另有19例AMAM2阳性患者进行肝穿病理检查时,12例(63.7%)患者病理提示符合PBC诊断.结论 自身抗体对PBC有诊断意义,注重自身抗体的检测对明确自身免疫性肝病有重要的临床意义.     

20例原发性胆汁性肝硬化自身抗体和免疫功能分析

背景:一般认为血清抗线粒体抗体M2亚型(AMA-M2)阳性是诊断原发性胆汁性肝硬化(PBC)的必备标准,但仍存在一定比例的AMA-M2阴性PBC患者。因此,了解PBC患者的自身抗体谱和免疫功能有助于PBC的诊断。目的:分析PBC患者的自身抗体和免疫功能,探讨其对PBC的诊断价值。方法:连续纳入确诊的PBC患者20例,以免疫印迹法检测肝特异性自身抗体,以间接免疫荧光法检测肝非特异性自身抗体,以免疫散射比浊法检测免疫球蛋白和补体;13例患者行肝穿刺活检组织病理学检查。结果:本组PBC患者女性多于男性(17:3),年龄39～75岁,平均57.2岁±2.1岁。肝特异性自身抗体中AMA-M2阳性最为多见(40%),其次为核点蛋白SP100抗体(15%)、肝肾微粒体1型(LKM-1)抗体(15%)、GP210抗体(10%)和肝细胞溶质抗原Ⅰ型(LC-1)抗体(10%);肝非特异性自身抗体以抗核抗体(ANA)检出率最高(70%);IgA、IgM和IgG升高者均占50%。结论:自身抗体,尤其是血清AMA-M2阳性是诊断PBC的重要依据之一,但多种蛋白在PBC病程中均有表达,且临床上有相当比例的AMA-M2阴性PBC患者。其他肝特异性自身抗体,如SP100抗体、GP210抗体等以及临床特点和肝穿刺活检对AMA-M2阴性PBC的诊断有重要价值。     

自身抗体联合检测在原发性胆汁性肝硬化诊断中的意义

目的探讨不同抗体联合检测在原发性胆汁性肝硬化(PBC)诊断中的意义。方法随机选择灵台县妇幼保健站2010年7月-2013年7月收治的肝病患者245例,根据患者所患疾病种类不同,将患者分为PBC组(n=162)、自身免疫性肝炎(AIH)组(n=42)和其他肝病患者(LDC)组(n=41)。采用ELISA法检测血清抗线粒体抗体M2亚型(AMA-M2)、抗SP100以及GP210抗体,采用Western Blot检测法检测血清中抗可溶性肝抗原(抗SLA)抗体,采用间接免疫荧光法检测血清抗线粒体抗体(抗AMA)。组间抗体阳性率的比较采用χ2检验和Fisher’s检验。结果 PBC患者的AMA、AMA-M2、抗GP210的阳性率分别是93.21%、87.65%、19.75%,高于AIH患者的19.05%、7.14%、9.52%,差异具有统计学意义(χ2=97.311,P=0.001;χ2=98.264,P=0.001;χ2=10.312,P=0.012)。PBC患者的AMA、AMA-M2及抗GP210的阳性率分别为93.21%、87.65%、19.75%,LDC患者的阳性率分别为9.76%、2.44%、7.32%,PBC患者明显高于LDC患者,差异具有统计学意义(χ2=142.745,P=0.003;χ2=112.574,P=0.002;χ2=15.217,P=0.042)。结论 AMA对PBC的诊断具有标志性意义,抗SP100对PBC的疾病进展具有提示作用,抗GP210对阴性PBC患者具有诊断作用。     

原发性胆汁性肝硬化特异性自身抗体的筛查和分析

目的 调查原发性胆汁性肝硬化(PBC)特异性自身抗体抗线粒体抗体(AMA)M2型、抗gp21t0和抗sp100在普通成人中的流行情况,并初步调查PBC的患病率.方法 以间接免疫荧光法初筛8126名体检者血清抗核抗体(ANA)及AMA,再用酶联免疫吸附法或Western blot检测ANA或AMA阳性血清中AMA-M2、抗sol00和抗gp210,最后结合临床表现和其他检查结果进行诊断.结果 8126名成年人中AMA阳性35例(0.43%,95%可信区间为0.30%～0.58%)、ANA79例(0.97%),两种抗体阳性率均随年龄的增长而增高.PBC特异性自身抗体阳性共22例,其中19例为AMA-M2阳性(0.23%),抗sp100阳性4例(0.05%),抗gp210阳性3例(0.04%).在PBC发病集中的40岁以上妇女中,PBC特异性自身抗体检出率为0.62%.22名PBC特异性自身抗体阳性者中只有1名女性最终被确诊为PBC.结论 PBC特异性自身抗体在普通成人中均较为少见,我国南方地区成人PBC患病率可能并不低于其他地区.     

原发性胆汁性肝硬化的诊断

原发性胆汁性肝硬化(PBC)是一种自身免疫性肝病,主要累及中年女性,最常见的症状为乏力和皮肤瘙痒,血清抗线粒体抗体(AMA),尤其是M2亚型(AMA-M2)阳性对诊断具有特异性.本文就PBC流行病学、临床表现、实验室检查、病理特征以及有关诊断标准进行了详细论述.     

原发性胆汁性肝硬化胆小管自身抗原的表达

原发性胆汁性肝硬化(PBC)是一种不明原因的自身免疫性肝病，组织学上表现为非化脓性破坏性胆管炎，门管区(特别是损伤的胆管周围)密集以T淋巴细胞为主的大量炎症细胞浸润，导致胆管上皮脱落、基底膜断裂。临床上以呈现血中高滴度抗线粒体抗体(AMA)和血清IgM含量升高为特征。胆管上皮细胞(BEC)自身抗原的表达可能与PBC免疫识别和胆管上皮损伤有关。     

原发性胆汁性肝硬化的实验室诊断研究进展

原发性胆汁性肝硬化是一种病因与发病机制至今未明的慢性进行性胆汁淤积性肝脏疾病,且目前尚无治愈的特效方法,早期给予熊去氧胆酸胶囊治疗可以改善肝脏功能,延长生命,一旦进入晚期则需肝移植治疗,所以早期诊断至关重要,本文就实验室诊断的一些新进展进行综述。     

原发性胆汁性胆管炎自身抗体的研究进展

原发性胆汁性胆管炎（PBC）是一种慢性、进行性、肝内胆汁淤积性疾病,其发生发展过程中伴随着自身抗体的滴度变化。然而,其发病机制尚不明确,自身抗体的变化幅度及其在PBC时发挥的作用尚未完全清楚。因此,目前缺乏对PBC患者早期明确诊断的有效方法。寻找特异性的PBC自身抗体标志物,将大大提高诊断效率,为早期开始治疗争取时间,...     

Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis

Although there have been significant advances in understanding the clinical and biochemical features of primary biliary cirrhosis (PBC), there is still a paucity of data on the usefulness of biomarkers as prognostic indicators. This is particularly important at the time of initial diagnosis. Indeed, the widespread use of antimitochondrial antibody testing has led to an earlier diagnosis of asymptomatic PBC and it is difficult to predict which patients will experience a benign versus a rapidly progressive course. To address this issue, we examined a unique population of 127 newly diagnosed patients with PBC during a 15-year period of observation that began in January 1990. Sera from these patients were analyzed for antimitochondrial, antinuclear, and anti-smooth muscle antibodies, and immunoblotting was performed for nuclear pore complex (NPC). The patients were then followed up longitudinally using biochemical liver function tests. No patient was under any medical therapy for PBC at the time of the initial sera collection. Data were analyzed based not only on the clinical features, but also the Mayo score and specific outcome measures, including time to death, need for liver transplantation, and complication free survival. Among patients with early disease, bilirubin increased to >2 mg/dL in the anti-NPC(+) patients (26% vs. 5%, P = .019). Anti-NPC antibodies remained stable or slightly increased over the period of observation. In condusion, anti-NPC identifies patients likely to experience an unfavorable clinical course and more rapid disease progression.     

原发性胆汁性肝硬化发病机制研究进展

原发性胆汁性肝硬化(primary biliary cirrhosis, PBC)的病因不清,国内外学者从多个角度入手对其发病机制进行了深入研究并提出了多个假设,取得了较大进展．PBC患者的家庭成员有较高的患病风险,且其一级亲属多伴有其他自身免疫性疾病;PBC与HLA Ⅱ型抗原关系较密切,但欧美各国与中国研究结果存在差异,说明PBC的遗传学与流行病学可能与地理分布有关;非HLA遗传因素单核苷酸多态性 (SNPs)在CTLA-4、IL、维生素D及细胞色素 P450等方面的研究都取得了不同进展;PBC易感性还可能与X连锁基因相关;近期利用重组丙酮酸脱氢酶复合物E2亚单位(PDC-E2)特异性二聚体IgA单克隆抗体(mAbs)杆状病毒表达系统对AMA进行的研究阐述了IgA在PBC 患者胆管上皮细胞(BECs)损伤中的作用,并提出了新的假设．对Sp 100的研究发现其对抗原始内皮细胞血管生成中的作用,与PBC的发病存在一定关系．近来不断有新的物质被鉴定与 PBC发病相关．     

表达SP100抗体的原发性胆汁性肝硬化患者的临床特点

目的 了解表达SP100抗体的原发性胆汁性肝硬化(PBC)患者的临床特点,为临床上诊断和随访PBC患者提供依据. 方法 回顾性分析70例PBC患者,分为抗SP100阳性组12例、抗SP100阴性组58例,比较其症状、肝功能、免疫学指标及肝病理组织学等特征.用SPSS11.5统计软件包进行数据的统计学处理,两组间均数比较采用成组资料t检验,非正态资料采用秩和检验,等级资料采用Ridit分析. 结果 抗SP100阳性组和抗SP100阴性组,在年龄、性别、临床表现、抗线粒体抗体M2亚型(AMA-M2)表达,差异均无统计学意义.碱性磷酸酶、γ-谷氨酰转肽酶中位数和IgM平均值抗SP100阳性组分别为466 U/L、728 U/L和(4.25±2.86) g/L,抗SP100阴性组分别为163U/L、154 U/L和(2.81±2.15) g/L,抗SP100阳性组碱性磷酸酶、γ-谷氨酰转肽酶和IgM水平均高于抗SP100阴性组,Z值分别为3.71和3.38、t=2.06,P值均＜0.05,差异有统计学意义.40例AMA-M2阴性的PBC患者中抗核抗体阳性18例,占45％,抗SP100阳性8例,占20％,AMA-M2阴性的PBC患者中抗核抗体阳性率高于抗SP100阳性率,P=0.021.AMA-M2表达在抗SP100阳性组和抗SP100阴性组间差异无统计学意义.病理组织学上,PBC各期患者均有SP100抗体表达.结论 表达SP100抗体的PBC患者的临床特征类似于未表达SP100抗体者;对SP100抗体表达的PBC患者更应重视随访.     

No prognostic significance of antimitochondrial antibody profile testing in primary biliary cirrhosis

BACKGROUND/AIMS: The rate of disease progression varies considerably between individuals with primary biliary cirrhosis (PBC). On the basis of serological subtyping 4 antimitochondrial antibody (AMA) profiles (A, B, C and D) can be defined. The finding of previous studies that profile C/D is associated with a progressive course, in contrast to profile A/B, is a question of debate. The aim of the study was to investigate whether AMA profiles predicted the course for a cohort of Dutch PBC patients. METHODOLOGY: Patients with an established diagnosis of AMA-positive PBC, AMA-negative PBC patients, non-PBC decompensated cirrhotics and healthy volunteers. Serum samples from 38 AMA-positive progressive patients, 31 AMA-positive patients without evidence of progression for at least 6 years, 5 AMA-negative PBC patients, 5 non-PBC decompensated cirrhotics and 5 healthy volunteers were assessed. AMA profiles were determined without knowledge of the clinical data. RESULTS: In the progressive AMA-positive group, 13% had profile A/B and 84% had profile C/D. In the non-progressive group, 13% had profile A/B, 77% profile C/D; 10% had no profile. During follow-up, a change from profile A/B to profile C/D or vice versa was not observed. CONCLUSIONS: This study found that not only PBC patients with AMA profile C/D but also patients with profile A/B may run a progressive course and therefore does not support the suggestion that AMA profiles can be used as independent prognostic indicator. The divergent results of this and previous studies may be explained by the selection of different patient populations.     

Malignancies in primary biliary cirrhosis

(Table is included in full-text article.)PBC in the advanced stage, corresponding to PBC stage IV, was shown in the past to be associated with an increased incidence of hepatocellular carcinoma (HCC). There is currently a debate, about the increase in incidence of extrahepatic malignancies, as some, but not all studies reported these neoplasms to be more common, especially breast cancer, irrespective of the PBC disease stage. In this issue of the journal a case series is reported on the incidence of various malignancies in a cohort of 212 patients with PBC from Greece. Considering as reference the cancer registries of another Mediterranean Country, like Italy, we could suggest that the incidence of extrahepatic malignancy, breast included, is not increased in PBC patients. Indeed, a more accurate analysis of the literature, shows that higher incidence of breast cancer were reported only for PBC patients evaluated in the 1970s and early 1980s, for whom a contribution of immunosuppressive agents, largely under investigation at that time, could be speculated. PBC patients do not need, therefore, to be submitted to stricter surveillance programs for extrahepatic cancer than the general population. As far as the development of HCC is concerned, instead, PBC patients should undergo the usual surveillance reserved to other categories of cirrhotic patients, according to published guidelines for the management of HCC. Such surveillance should start only when PBC patients have reached disease stage IV (frank cirrhosis).     

Fatigue in primary biliary cirrhosis

The autoimmune liver disease, primary biliary cirrhosis (PBC), is associated with debilitating fatigue in a significant proportion of patients. The pathogenesis of fatigue in PBC is unclear, but preliminary studies suggest it has central mechanisms and may have peripheral manifestations. Studies are beginning to elucidate the biological associates of fatigue in PBC, particularly sleep disturbance and autonomic dysfunction. Comprehensive studies investigating the pathogenesis of fatigue in PBC are urgently needed as are large-scale prospective outcome studies.     

Asymptomatic primary biliary cirrhosis

Four asymptomatic patients are described with raised serum alkaline phosphatase values and a positive serum mitochondrial antibody test. In all four needle liver biopsy showed destructive bile duct lesions. Lymphocyte transformation to phytohaemagglutinin was normal in three and impaired in one who also suffered from rheumatoid arthritis. Two patients showed normal skin and serological test responses to dinitrochlorobenzene and haemocyanin.These four patients are believed to be suffering from asymptomatic primary biliary cirrhosis.