自身免疫性肝病的自身抗体检测及报告规范

自身抗体对自身免疫性肝病的诊断非常重要。抗线粒体抗体（AMA）及AMA-M2抗体是原发性胆汁性肝硬化（PBC）的诊断指标之一,具早期诊断作用,但与疗效和预后无相关性。PBC患者抗核抗体（ANA）有一定荧光模式,抗sp100和抗gp210对PBC有很高特异性。大部分自身免疫性肝炎（AIH）所出现的自身抗体缺乏疾病特异性,ANA和抗平滑肌抗体也可见于其他多种肝病。参照自身抗体将AIH分为两型,抗-SLA对AIH有极高特异性,阳性者病情多较重。自身抗体主要检测方法为间接免疫荧光法（IIF）、ELISA和免疫印迹法。ANA标准检测程序应为：IIF法对标本筛查,而后对必要者进行特异性ANA谱定量或半定量检测。自身抗体的室间质量评价是质量控制措施之一。     

自身免疫性肝炎中的自身抗体及自身抗原

自身免疫性肝炎 (ＡＩＨ)是一组不明原因、具有相似临床表现的慢性免疫性肝病 ,以免疫学指标如高丙种球蛋白和自身抗体为特征。同时 ,它亦是一些激发因子、自身抗原、遗传倾向和免疫调节网络之间错综复杂的相互作用而打破自身耐受 ,由自身免疫反应导致的持续性肝细胞损害的结果。自 195 0年Ｗａｌｄｅｎｓｔｒｏｍ首次报道ＡＩＨ以来 ,根据血清自身抗体谱把ＡＩＨ分成 3个血清学亚型 :Ⅰ型ＡＩＨ ,抗核抗体 (ＡＮＡ )或 (和 )抗平滑肌抗体 (ＳＭＡ)阳性 ;Ⅱ型ＡＩＨ ,抗肝肾微粒体 (ＬＫＭ )Ⅰ型抗体阳性 ;Ⅲ型ＡＩＨ ,抗可溶性肝抗原 /肝胰…     

自身免疫性肝病自身抗体研究进展

自身免疫性肝病（ALD）是一组免疫介导的肝脏损伤,根据其临床表现、生化、免疫学、影像学和组织病理学特点,可简单分为以肝炎为主型,即自身免疫性肝炎（AIH）和以胆系损害及胆汁淤积为主型,即原发性胆汁性肝硬化（PBC）、原发性硬化性胆管炎（PSC）。此外,还有这三种疾病中任意两者之间的重叠综合征（overlap syndromes）,主要以AIH—PBC重叠综合征多见。由于我国肝炎和肝硬化多因肝炎病毒,尤其是乙型肝炎病毒引起,故过去认为ALD较少见。     

自身免疫性肝病患者自身抗体免疫学特点分析

我们对自身免疫性肝病患者血清中出现循环的自身抗体进行分析,探讨自身抗体在鉴别自身免疫性肝病及病毒性肝炎中免疫学之间的关系。一、资料与方法1.研究对象:收集2000年10月至2005年6月来我院门诊及入院就诊的肝功能生化指标。ALT≥40 U/L,且反复异常,HBsAg阴性的3500例患者。参照国际自身免疫性肝炎组修订的评分标准和美国肝病学会原发性胆汁性肝硬化(PBC)指导建议,结合相关临床资料及部分患者肝组     

自身免疫性肝病相关自身抗体检测的临床应用专家共识

自身免疫性肝病是一组由异常自身免疫介导的肝胆炎症性疾病,主要包括自身免疫性肝炎、原发性胆汁性胆管炎、原发性硬化性胆管炎及上述任何两种疾病主要特征同时出现的重叠综合征等。自身免疫性肝病相关自身抗体检测临床应用的标准化,有助于疾病的诊断与分类、预测预后、病情监测及发病机制的研究。     

肝功能异常患者中自身抗体及自身免疫性肝病的检测

目的 自身免疫性肝病临床流行病学调查,观察在肝功能异常患者中自身抗体检测的阳性率、自身免疫性肝病检出率及临床意义。方法 连续收集就诊病例中肝功能异常患者丙氨酸氨基转移酶(ALT)大于40 U/L血清511份,分别进行相关自身抗体(ANA)检测,并查阅临床资料。结果 511份血清检测出ANA阳性率为14.09％,抗平滑肌抗体(SMA)阳性率0,59％,抗线粒体抗体(AMA)阳性率2.94％,抗线粒体抗体亚型-丙酮酸脱氢酶复合物(AMA-M2)阳性率0.98％;ANA谱中的SS-A阳性率0.59％、SS-B阳性率0.20％、JO-1阳性率0.20％,dsDNA阳性率0.78％;未检出抗肝肾微粒体抗体(LKM-1)、可溶性肝抗原/肝胰抗原(SLA/LP)、抗肝细胞溶质抗原1型抗体(LC-1)及ANA谱中其他抗体。从ALT升高的患者中收集到的511份血清,可查到完整临床资料者共469例。原发性胆汁性肝硬化(PBC)及自身免疫性肝炎(AIH)患者检出率分别为1.06％及0.43％,未检出原发性硬化性胆管炎患者。自身抗体阳性患者77.78％诊断为病毒性肝炎及相关疾病。病毒性肝炎及相关疾病中自身抗体阳性率为18.29％。结论 高滴度(>1:320)自身抗体对自身免疫性肝病诊断有意义。PBC及AIH患者检出率近似丙型及戊型肝炎检出率,临床不能忽视,病毒性肝炎及相关疾病中可检测出自身抗体。     

自身免疫性肝病43例临床分析

目的比较自身免疫性肝炎（AIH）与原发性胆汁性肝硬化（PBC）的临床及实验室检查特点,以利于临床早期诊断及鉴别诊断。方法对26例AIH患者、17例PBC患者的临床和实验室检查资料进行回顾性分析。结果 AIH与PBC多发于中年女性,AIH患者肝功能异常以转氨酶增高为主,PBC以总胆红素、碱性磷酸酶、γ-谷氨酰转肽酶升高为特点,AIH中可出现多种自身抗体异常,以抗核抗体为主,而PBC患者以抗线粒体抗体及其分型M2异常为主。结论 AIH及PBC的诊断可结合临床、生化、自身抗体检查的结果,其中自身抗体的检测尤为重要。     

甲状腺自身免疫性抗体与丙型肝炎病毒感染的相关性分析

目的 探讨自身免疫性甲状腺病、甲状腺自身抗体与HCV感染的相关性.方法 选取甲状腺过氧化物酶抗体(TPOAb)和(或)甲状腺球蛋白抗体(TgAb)阳性者462例,分别选取年龄和性别匹配的TPOAb和TgAb阴性者380例作为对照,检测血清抗-HCV,阳性者进一步作HCVRNA定性检测.同时,选取临床诊断的195例丙型肝炎患者作病例组,并选取年龄和性别匹配的150名健康人和150例乙型肝炎患者作对照组,行甲状腺相关指标的测定.采用独立样本t检验和X2检验.结果 甲状腺自身抗体阳性组462例患者中,HCV感染阳性率为1.30%,阴性组380例中HCV感染阳性率为0.53%,差异无统计学意义(X2=1.322,P>0.05).丙型肝炎患者的TPOAb阳性率为30.8%,TgAb阳性率为30.8%,均显著高于乙型肝炎患者和健康人(X2=21.496,X2=30.454; P<0.01).结论 甲状腺自身免疫异常者未见HCV感染率增高,而丙型肝炎患者甲状腺自身抗体阳性率增高,提示丙型肝炎患者应注意检测甲状腺相关指标.     

辅助用药在自身免疫性肝病中的应用

自身免疫性肝病是一组由自身免疫介导的肝胆系统性疾病,主要包括自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)和原发性硬化性胆管炎(PSC).由于其病因和发病机制尚未完全阐明,目前尚无治愈性药物.现简要介绍临床实践指南推荐的标准治疗方案,并讨论抗炎保肝药在自身免疫性肝病辅助治疗中的应用情况.     

Presence of antimitochondrial autoantibodies in patients with autoimmune hepatitis

BACKGROUND AND AIM: Antimitochondrial autoantibodies (AMA) are known to be a hallmark of primary biliary cirrhosis, and it has been suggested that AMA play a crucial role in generating biliary changes. Biliary tract lesions are not uncommon in patients with autoimmune hepatitis (AIH) and previous works have demonstrated that AMA are occasionally detectable in sera of patients with AIH. Therefore, the role of AMA as a cause of bile duct lesions in AIH livers should be addressed. The aim of the present study was to determine whether the presence of AMA is associated with clinical features, especially the occurrence of bile duct lesions, in patients with AIH. METHODS: Forty-one patients diagnosed as having AIH according to the revised scoring system of the International Autoimmune Hepatitis Group were enrolled in this study. Clinical data were retrospectively reviewed, and histological findings of the liver were investigated. AMA reactivity was determined by immunoblotting using beef heart mitochondria as antigens. RESULTS: Although not found in any enrolled patient by conventional indirect immunofluorescence, AMA were detectable in 14 out of 41 patients (34%). Clinical parameters including biochemistry, autoantibody profile, and responses to treatment were similar irrespective of AMA status. Bile duct lesions were noted in 14/14 (100%) and 23/27 (85%) of AMA-positive and -negative patients with AIH, respectively (P = 0.134). There was no statistically significant difference in the grade of inflammation or stage of fibrosis between the two groups. CONCLUSION: Antimitochondrial autoantibodies were found to be present in sera of patients with AIH more frequently than expected, even at very low titer. However, clinical features and histological findings of AIH were not influenced by the AMA status.     

自身免疫性肝病基础和临床研究进展

自身免疫性肝病与常见肝病的差异性较大,提高其认知度和诊断水平尤为重要。回顾了有关自身免疫性肝病最近几年的文献资料,总结了自身免疫性肝病的发病机制、自身抗体、诊断及治疗方面取得的进展,指出还须进一步的临床研究及实践加以证实和完善。     

Celiac disease autoantibodies in severe autoimmune liver disease and the effect of liver transplantation

Background/aims: Celiac disease (CD) is associated with primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. We investigated the following: (i) the prevalence of tissue transglutaminase antibodies (tTGAs) and endomysial antibodies (EMAs) in end‐stage autoimmune liver disease (ESALD), (ii) the correlation among auto‐antibodies and the human leucocyte antigen (HLA) haplotype, and (iii) the effect of liver transplantation on antibody kinetics. Methods: Pretransplantation sera from 488 patients (310 with ESALD, and 178 with non‐autoimmune disease) were tested for tTGAs. Positive samples were also tested for EMAs, and retested 6–12 and ≥24 months post‐transplantation. Results were correlated with the HLA type of the recipient. Results: Serological evidence of CD was found in 3% (ESALD) vs. 0.6% (non‐autoimmune) of the patients (five‐fold increased risk in ESALD). The prevalence of tTGAs (14.2 vs. 5.4%, P=0.0001) and EMAs (4.3 vs. 0.78%, P=0.01) was significantly higher in patients with the HLA‐DQ2 or HLA‐DQ8 haplotypes. tTGAs and EMAs normalized in 94 and 100%, respectively, without gluten exclusion post‐transplantation. Post‐transplantation, of the five patients with symptoms of ‘classical’ CD, three improved. Intestinal lymphoma was diagnosed in another two cases with clinically ‘silent’ CD. Conclusions: Patients with ESALD, especially those who are HLA‐DQ2 or HLA‐DQ8 positive had a high prevalence of CD‐associated antibodies. Both tTGAs and EMAs decreased post‐transplantation without gluten withdrawal. Immunosuppression may improve symptoms of CD, but might not prevent progression to intestinal lymphoma.     

Autoimmune serology in liver disease: methodology and interpretation

Abstract   Accurate measurement of levels of autoantibodies in serum is critical for the diagnosis of autoimmune hepatitis. The major reactivities include anti-nuclear antibody (ANA), smooth muscle antibody (SMA), antibody to liver kidney microsomes type-1 (anti-LKM1); other relevant reactivities include antibodies to liver cytosol 1 (anti-LC1), soluble liver antigen (anti-SLA), and neutrophil cytoplasmic antigens (ANCA). In addition to the classical indirect immunofluorescence technique, automatic assays based on recombinant antigens are now available, which allow detection of antibodies not visible on immunofluorescence, like anti-SLA, and assist in the interpretation of at times problematic immunofluorescence patterns, like anti-LKM1 or anti-LC1.     

儿童自身免疫性肝病

儿童自身免疫性肝病是一种由自身免疫反应介导的慢性进行性肝脏疾病,包括自身免疫性肝炎、自身免疫性硬化性胆管炎、肝移植后新发自身免疫性肝炎。近年来儿童自身免疫性肝病的发病率逐渐上升,但临床表现缺乏特异性,有不同于成人的临床特点,现有的IAIHG积分系统并不适合儿童患者,故临床上容易误诊或漏诊。及时应用免疫抑制剂治疗至关重要,可明显改善预后。本文主要对该病的诊治研究进展进行综述。     

Complement-fixing platelet autoantibodies in autoimmune thrombocytopenia

A 16-year-old male patient is described with chronic autoimmune thrombo-cytopenic purpura and, after two years, “warm” autoimmune hemolytic anemia (Evans syndrome) who transiently developed complement-fixing platelet autoantibodies. The autoreactivity of these antibodies was established by quantitative complement fixation as well as by absorption and elution studies using autologous platelets. We believe this to be the first documented case with this very rare and peculiar type of platelet autoantibody.     

Molecular mimicry and autoimmune liver disease: virtuous intentions,malign consequences

Abstract: The pathogenesis of autoimmune liver disease and autoimmunity associated with chronic viral hepatitis remains poorly understood. One of the major hurdles to a deeper understanding of these pathological processes is the absence of clearly defined inductive mechanisms, which, if identified and characterised, could guide clinical strategies for their prevention or allow therapeutic intervention. Molecular mimicry leading to crossreactive autoimmune responses has gained strong experimental support in the past decade. A fundamental premise of this hypothesis is the involvement of a mimicking environmental trigger. In view of the numerous viral and bacterial agents epidemiologically linked to autoimmune liver diseases, we and others have proposed molecular mimicry to be an important mechanism in these diseases. We also propose similar crossreactive mechanisms to operate in the generation of autoimmunity in viral hepatitis. This review focuses on molecular mimicry at the level of the B‐cell, as few data on T‐cell crossreactivity in liver disease are thus far available.     

自身免疫性糖尿病相关抗体检测的研究进展

自身免疫性糖尿病以T细胞介导的胰岛β细胞特异性损伤及循环中出现胰岛自身抗体为特征,自身免疫是其发病的中心环节,自身抗体是目前最可靠的1型糖尿病（T1DM）生物标志物,临床应用广泛,其中最值得关注的则是其在T1DM的诊断及预测方面的价值。胰岛素自身抗体种类繁多,各有特点,目前临床应用的主要抗体包括谷氨酸脱羧酶抗体（GADA）、胰岛素自身抗体（IAA）、胰岛素瘤相关蛋白2抗体（IA-2A）和锌离子转运蛋白8抗体（ZnT8A）。联合检测对T1DM的诊断及预测有重要意义。     

自身免疫性肝炎的诊断和治疗

自身免疫性肝炎(autoimmune hepatitis,AIH)是一种累及肝脏实质的特发性疾病.临床上,AIH以高血清转氨酶、高γ-球蛋白/Ig、高滴度自身抗体和肝组织学上以界面性肝炎(interface hepatitis)为特点,但需排除其他原因所致慢性肝病的可能.该病一般对糖皮质激素治疗应答良好.基于血清免疫学发现,AIH可分为二型:Ⅰ型AIH是最常见的疾病类型,与抗核抗体(ANA)和/或平滑肌抗体(SMA)、抗肌动蛋白抗体、非典型P-ANCA及抗可溶性肝抗原/肝胰抗体(抗SLA/LP)等有关;Ⅱ型AIH主要发生于儿童,以抗肝/肾微粒抗体1型(抗LKM -1)和抗肝细胞溶质-1抗体(抗LC-1)为主.大约有10％的患者血清自身抗体可呈阴性.按基因型可分为HLADR3( DRBI^0301)、HLA -B8和HLA - DR4CDRBI^0401,0405)等类.在存在相应的组织学改变的基础上,AIH的诊断还需结合临床和生化特点、血清自身抗体和免疫球蛋白水平.