MPO、ANCA、SMA及ANA抗体联合检测对自身免疫性肝炎的诊断意义

检测56例自身免疫性肝炎(AIH)患者、176例非AIH及40例健康体检者中抗髓过氧化物酶(MPO)抗体、抗核抗体(ANA)、抗平滑肌抗体(SMA)和抗中性粒细胞胞质抗体(ANCA)等自身抗体表达.结果 AIH组患者MPO、ANA、SMA及ANCA抗体检出率均明显高于其他非AIH患者及对照组(P均＜0.01).认为MPO抗体联合ANA、SMA及ANCA的检测对诊断、治疗和阻止AIH的发展有着十分重要作用.     

自身免疫性肝炎的研究进展

自身免疫性肝炎(AIH)是一种病因不明，以肝脏门静脉周围病变为主的慢性炎症病变，同时外周血中常存在各种自身抗体及高球蛋白血症。根据血清中抗体的不同类型，可将AIH分为不同的亚型。近年来，国际上对AIH的研究十分活跃，并且制定了新的临床诊断评分标准。AIH在我国并非少见，但许多临床医师对它缺乏足够的认识，使不少AIH患者得不到及时的诊断和治疗。现将AIH的研究进展综述如下。     

自身免疫性肝炎相关自身抗体及临床意义

自身免疫性肝炎(AIH)是一种靶向肝细胞、自身免疫反应介导的肝脏实质炎症,以血清中存在自身抗体及高IgG和(或)高γ-球蛋白血症为特征。大多数AIH患者血清中存在一种或多种自身抗体,这些自身抗体是AIH的重要特征和诊断的重要依据,部分自身抗体还与AIH的不同临床表现、疾病活动、治疗应答以及预后相关。对AIH相关自身抗体及其临床意义进行了探讨。     

体检肝功能异常诊断自身免疫性肝炎1例并文献复习

<正>自身免疫性肝炎(autoimmune hepatitis, AIH)是由异常自身免疫介导累及肝细胞的实质炎症反应,因其病程长,疾病初期无特异性症状顾不易察觉,极易漏诊误诊。现报道1例仅以血清转氨酶活性升高为首发表现确诊AIH病例,以提高重视自身抗体对AIH及早诊断的效益。1 病例介绍患者女,47岁,主诉3年前体检发现肝酶指标升高,未予重视。今年再次体检仍示谷丙转氨酶(ALT)、谷草转氨酶(AST)指数较前上升,     

自身免疫性肝炎患者自身抗体的测定及意义

目的:探讨自身抗体测定对诊断自身免疫性肝炎的临床意义．方法:采用间接免疫荧光法(IIF)检测47例自身免疫性肝炎患者、158例非自身免疫性肝炎患者及40例健康体检者体内抗核抗体(ANA)、抗平滑肌抗体(SMA)、抗中性粒细胞胞质抗体(ANCA)、抗线粒体抗体(AMA)等自身抗体,ELISA法检测抗MPO抗体,并对结果进行回顾性分析．结果:ANA、SMA及ANCA检出率的比较,结果显示AIH中阳性率最高为SMA(66．0％, 31／47),而非AIH中则为6．3％(10／158),两组差异有非常显著性意义(P<0．01)．经X2检验, SMA、AMA和MPO抗体检测在AIH与PBC中,均有非常显著性意义(P<0．01)．AIH各型自身抗体检测结果表明,AIH-Ⅰ与ANA、SMA和ANCA相关,AIH-Ⅱ与LKM相关,而AIH=Ⅲ与SLA和ANCA相关．结论:血清自身抗体的检测对诊断、治疗和阻止自身免疫性肝炎的发展有着十分重要作用,对提高AIH在临床上同其他肝病鉴别诊断和治疗有着非常重要的意义．     

自身免疫性肝病20例临床特点分析

目的　比较自身免疫性肝炎 (AIH)、原发性胆汁性肝硬化 (PBC)和原发性硬化性胆管炎 (PSC)的临床特点 ,以利于临床早期鉴别诊断。方法　分析我院 1998～ 2 0 0 1年 2 0例自身免疫性肝病 (AIH 9例 ,PBC 10例 ,PSC 1例 )的临床资料 ,并对其肝功能特点及自身抗体进行比较。结果　 2 0例患者中 ,男女之比为 2∶18,平均年龄 (5 4.7± 11.0 )岁。AIH与PBC患者各项指标比较 ,PBC肝功能异常以碱性磷酸酶升高为特点 ,其余指标比较差异无显著性 ;AIH免疫学指标以γ 球蛋白、主要是免疫球蛋白IgG升高为特点 ,而PBC以γ 球蛋白、主要是IgM升高为特点 ;AIH循环自身抗体以抗核抗体、抗平滑肌抗体为主 ,而PBC患者以抗线粒体抗体及其分型M2 为主。结论　AIH及PBC临床表现、肝功能检查有许多相似之处 ,但仍然有其各自特异的临床诊断依据     

以慢加急性肝衰竭起病的自身免疫性肝炎1例报告

<正>自身免疫性肝炎（AIH）是一种由针对肝细胞的自身免疫反应所介导的肝脏实质炎症，其临床表现多样，一般表现为慢性、隐匿起病，但也可表现为急性发作，甚至引起急性肝衰竭。现报道1例临床少见的以慢加急性肝衰竭为表现的AIH患者，以提升对AIH特殊临床表型的认识。     

西南地区三种自身免疫性肝病的临床特点分析

目的：分析西南地区各型自身免疫性肝病的临床特点,以期提高早期诊断率。方法回顾性分析比较第三军医大学西南医院收治的436例自身免疫性肝病患者的一般资料、临床表现、血清生化学、自身抗体、肝组织病理等指标的差异,其中包括自身免疫性肝炎（AIH）211例,原发性胆汁性肝硬化（PBC）145例,自身免疫性肝炎-原发性胆汁性肝硬化重叠综合征（OS）80例。结果患者平均发病年龄为49．7岁,男女比为1∶6;各组临床表现无显著差异;各组 ALT、GGT、TBil等血清学指标差异有统计学意义（P＜0．05）;AIH 组血清自身抗体以ANA（＋）为主,PBC 组中以AMA（＋）、AMA-M2（＋）为主,OS组兼有AIH 及PBC自身抗体的特点;各组肝组织病理主要表现为肝细胞变性、坏死、炎细胞浸润、小胆管炎症及纤维增生。结论在我国西南地区AIH、PBC、OS多为50岁左右的围绝经期女性。综合分析临床表现、血清生化学指标、免疫球蛋白亚型、自身抗体等指标有助于确诊不同类型的自身免疫性肝病,肝活组织检查为重要的辅助诊断手段。     

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。     

自身免疫性肝炎的现代处理观点

自身免疫性肝炎（AIH）常见于女性,表现为肝酶异常（转氨酶升高）、血清自身抗体如抗核抗体（ANA）、抗平滑肌抗体（SMA）、抗可溶性肝抗原抗体／肝胰抗原（SLA／LP）、抗肝肾做粒体抗体（LKM）1阳性和γ-免疫球蛋白升高,但并非所有AIH患者均出现上述特征。AIH的组织学特点为界面性肝炎,以浆细胞和淋巴细胞浸润为主,但无特征性组织学表现。AIH的确诊较为困难,目前的流行病学资料中报道的AIH实际发病率和患病率可能偏低。     

Neutralization Interfering Antibodies: A “Novel” Example of Humoral Immune Dysfunction Facilitating Viral Escape?

The immune response against some viral pathogens, in particular those causing chronic infections, is often ineffective notwithstanding a robust humoral neutralizing response. Several evasion mechanisms capable of subverting the activity of neutralizing antibodies (nAbs) have been described. Among them, the elicitation of non-neutralizing and interfering Abs has been hypothesized. Recently, this evasion mechanism has acquired an increasing interest given its possible impact on novel nAb-based antiviral therapeutic and prophylactic approaches. In this review, we illustrate the mechanisms of Ab-mediated interference and the viral pathogens described in literature as able to adopt this “novel” evasion strategy.     

Anti-endomysial Antibody Negative Celiac Disease

Anti-endomysium antibodies (AEM) fail to identify all untreated celiac disease (CD) patients. This study aims to determine if additional serology, in particular, IgA anti-tissue transglutaminase (tTG) antibodies, increases detection. Fifty-three biopsy-proven untreated CD patients (39 women, 14 men; median age 51 years) and 65 control patients with normal duodenal histology (46 women, 19 men; age range 17–90 years, median 45 years) were prospectively studied. Serum total IgA, IgA anti-tTG, IgA AEM, IgA anti-gliadin (AGA) and IgG AGA antibodies were measured. Thirteen (25%) CD patients were AEM negative. None were IgA deficient. Three AEM-negative CD patients had a raised IgA anti-tTG and IgA AGA. IgG AGA was raised in 10 AEM-negative CD patients, but also in 14/65 (22%) of controls. In conclusion, AEM-negative CD is common and detection is only modestly enhanced by testing for IgA anti-tTG antibodies. Duodenal biopsy is still recommended for the accurate diagnosis of CD.     

Atypical autoantibodies in patients with primary Sjögren syndrome: clinical characteristics and follow-up of 82 cases

OBJECTIVES: To analyze the clinical characteristics, follow-up, and fulfillment of classification criteria for other systemic autoimmune diseases (SAD) in patients with primary Sj?gren syndrome (SS) and atypical autoantibodies. METHODS: We studied 402 patients diagnosed with primary SS seen consecutively in our Department since 1994. We considered anti-DNA, anti-Sm, anti-RNP, anti-topoisomerase1/Scl70, anticentromere (ACA), anti-Jo1, anti-neutrophil cytoplasmic antibodies (ANCA), anticardiolipin antibodies (aPL), and lupus anticoagulant as atypical autoantibodies. The patients were prospectively followed after inclusion into the protocol, focusing on the development of features that might lead to the fulfillment of classification criteria for additional SAD. As a control group, we selected an age-sex-matched subset of patients with primary SS without atypical autoantibodies. RESULTS: Eighty-two (20%) patients showed atypical autoantibodies (36 had aPL, 21 anti-DNA, 13 ANCA, 10 anti-RNP, 8 ACA, 6 anti-Sm, 2 anti-Scl70, and 1 anti-Jo-1 antibodies). There were 77 (94%) women and 5 (6%) men, with a mean age of 57 years. Patients with atypical autoantibodies had no statistical differences in the prevalence of the main sicca features, extraglandular manifestations (except for a higher prevalence of Raynaud's phenomenon, 28% versus 7%, P=0.001), immunological markers, and in the fulfillment of the 2002 classification criteria, compared with the control group. After a follow-up of 534 patient-years, 13 (16%) of the 82 patients with atypical autoantibodies developed an additional SAD (systemic lupus erythematosus in 5 cases, antiphospholipid syndrome in 4, limited scleroderma in 3, and microscopic polyangiitis in 1) compared with none in the control group (P<0.001). CONCLUSIONS: This study shows an immunological overlap (defined by the presence of autoantibodies considered typical of other SAD) in 20% of our patients with primary SS. However, the clinical significance of these atypical autoantibodies varies widely depending on the autoantibodies detected, with a broad spectrum of prevalence and clinical patterns of disease expression, and a specific predilection for association with some SAD in preference to others.     

抗核小体抗体与抗C1q抗体在狼疮肾炎血清的表达及其临床意义

目的探讨抗核小体抗体与抗C1q抗体在狼疮肾炎（lupus nephritis，LN）患者血清的表达及其临床意义。方法使用酶联免疫吸附试验（ELISA）对46例LN患者血清进行检测，并与31例无肾炎临床表现的SLE患者作对照。结果LN患者血清中抗核小体抗体与抗C1q抗体浓度及阳性率显著高于SLE对照组（P〈0．01）。抗双链DNA（dsDNA）抗体、抗Sm抗体、抗nRNP抗体、抗心磷脂（aCL）IgG抗体有较高的阳性率，与对照组相比差异有统计学意义（P〈0．05）。将抗核小体抗体、抗C1q抗体、抗dsDNA抗体、抗Sm抗体、抗nRNP抗体和aCLIgG抗体分别引入Logistic回归进行统计分析，结果显示入选的自变量包括抗核小体抗体、抗C1q抗体、抗dsDNA抗体（P〈0．05）。结论在LN患者中，存在着抗核小体抗体、抗C1q抗体的高表达。抗核小体抗体及抗C1q抗体在LN发病中起重要的作用。抗核小体抗体、抗C1q抗体、抗dsDNA抗体是反映SLE患者并发肾脏损害的重要指标，在LN诊断和判定其活动性方面有重要作用。     

Anti-chromatin and anti-histone antibodies in Egyptian patients with systemic lupus erythematosus

There has been a renewed interest in anti-chromatin and anti-histone antibodies in the last few years. To assess the prevalence of anti-chromatin and anti-histone antibodies in patients with systematic lupus erythematosus (SLE) and to correlate serum levels of these antibodies with clinical features of the disease, the presence of anti-chromatin and anti-histone antibodies in 38 patients with SLE was investigated by an enzyme-linked immunosorbent assay (ELISA). To determine the specificity of these antibodies, 15 patients with rheumatoid arthritis, 15 patients with systemic sclerosis, and 15 normal controls were also tested. Sensitivity of anti-chromatin antibodies in SLE patients was 89.5% and specificity was 80.0%, while sensitivity of anti-histone antibodies was 92.1% and specificity was 82.2%. Significant associations were found between the levels of anti-chromatin antibodies and arthritis, malar rash, oral ulcer, pulmonary affection (P < 0.05) also, lupus nephritis (P < 0.01), and disease activity score as measured by SLE disease activity index (SLEDAI; P < 0.001). Significant association was found between anti-histone antibodies and fatigue (P < 0.05). The incidence of positive anti-chromatin and anti-histone antibodies was significantly higher than that of anti-dsDNA antibodies in early stage of the disease. We conclude that anti-chromatin and anti-histone antibodies are both sensitive and specific for SLE and could be a useful addition to the laboratory tests that can help in the diagnosis of SLE. Anti-chromatin antibodies seem to be a promising marker useful in early diagnosis and assessment of disease activity in SLE patients especially in patients who are negative for anti-dsDNA antibodies. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Autoantibodies in Chronic Pancreatitis

In 60 consecutive patients clinically suspected of having chronic pancreatitis the serum concentration of the immunoglobulins (IgA, IgG, IgM), the IgG- and IgA-type non-organ-specific autoantibodies against nuclear material (ANA), smooth and striated muscle, mitochondria, basal membrane, and reticulin, and the IgG- and IgA-type pancreas-specific antibodies against islet cells, acinus cells, and ductal cells (DA) were estimated blindly. In 23 of the patients chronic pancreatitis was verified, whereas chronic pancreatitis was rejected in 37 patients (control group). IgG and IgA were found in significantly higher concentrations in the patients with chronic pancreatitis than in the control group but within the normal range. ANA and DA occurred very frequently in both groups but with no statistical difference. Other autoantibodies only occurred sporadically. The findings of this study do not support the view of an immunological pathogenesis in chronic pancreatitis.     

甲状腺过氧化物酶抗体球蛋白抗体微粒体抗体在甲状腺自身免疫性疾病中的改变

目的 观察甲状腺过氧化物酶抗体(TPO Ab)、甲状腺球蛋白抗体(TG Ab)和甲状腺微粒体抗体(TM Ab)在自身免疫性甲状腺疾病(AITD)中的改变,探讨TPO Ab在临床诊断和治疗上的作用和意义.方法 收集AITD患者,根据甲状腺功能不同分为甲状腺功能亢进(简称甲亢)组(Graves病、GD,57例)、甲低组(桥本氏甲状腺炎、HT,48例)、亚甲低组(41例)和AITD复诊组(甲状腺功能恢复正常1～6个月,41例).另取一级亲属无GD或HT的健康人群53例为对照组.采用放射免疫分析法检测血清中甲状腺自身抗体(TPO Ab、TG Ab和TM Ab)及甲状腺激素和促甲状腺激素(FT3、FT4,sTSH)水平.结果 甲亢组、甲低组和亚甲低组中TPO Ab阳性率(87.70%、97.20%、100.00%)均明显高于同组内TG Ab阳性率(43.90%、60.42%、48.78%)和TM Ab阳性率(43.90%、79.10%、60.98%);3种甲状腺自身抗体的阳性率和阳性患者的抗体水平均高于相应的对照组.AITD复诊组的TPO Ab阳性患者的抗体水平[(683.04±606.55)kU/L]明显低于甲亢组、甲低组和亚甲低组[(1049.31±941.00)、(106 440.79±272.38)、(5133.01±4449.67)kU/L].结论 TPO Ab在AITD的诊断更具有代表意义,抗体水平为AITD治疗及预后评估提供了重要的依据.     

Transfusion-related acute lung injury and leucocyte-reacting antibodies

BACKGROUND AND OBJECTIVES: Transfusion-related acute lung injury (TRALI) is underdiagnosed and underreported. This is why we present cases suspected for TRALI, in which leucocyte antibodies were examined. MATERIAL AND METHODS: We analysed 44 patients with respiratory insufficiency, related to transfusion, who met criteria of acute lung injury (ALI). Lymphocyte and granulocyte antibodies were examined in donors and patients by six methods. RESULTS: Based on recent trends, we divided patients into two groups: TRALI (without risk factors for ALI) and possible TRALI (with probable risk factors). The incidence of antibodies was 68.2%, the majority were human leucocyte antigen (HLA) class I and/or II, the minority were non-specific granulocyte antibodies; half of all detected antibodies, however, reacted with granulocytes. Antibodies were found in 17 donors (more often in TRALI than in possible TRALI) and in 19 patients (in four - suspected to be of the donor origin, which would diminish the number of antibodies to 15). In seven available cases, we observed cognate antigen and/or positive cross-match. In the majority of patients, TRALI occurred after transfusion of red cells, in 56.2%- stored above 14 days; all the units were non-leucoreduced. Lookback in two donors showed that transfusions in 20 patients did not result in reported TRALI, even in the patient with cognate antigen. CONCLUSIONS: Our clinical observations suggest that to distinguish between TRALI and possible TRALI is difficult and the results are equivocal - it is worth considering whether it can be omitted. We have confirmed that antibodies are involved in TRALI, although their role is very complex. The role of stored red blood cells in the development of TRALI requires further observations in comparison with a control group of patients without TRALI.     

Follow-up of Patients Positive in Reticulin and Gliadin Antibody Tests with Normal Small-Bowel Biopsy Findings

Twenty-five patients with positive serum reticulin or gliadin antibody titres and having normal small-bowel mucosal villous architecture were re-biopsied after a follow-up period of 1 to 7 years. Seven were found on control examination to have small-bowel villous atrophy. At the initial examination, when coeliac disease was ‘excluded’, they thus belonged to the entity latent coeliac disease. Morphometrically minor mucosal changes in the initial biopsy specimen, suggesting an ongoing process, were seen in only three of them. Especially the serum IgA-class reticulin antibody test was a good predictor of latent coeliac disease. This study implies that patients with so-called false-positive IgA-class reticulin or gliadin antibody test should be re-examined.     

Screening for autoantibodies in chronic hepatitis C patients has no effect on treatment initiation or outcome

Autoantibodies in hepatitis C virus–infected patients may indicate autoimmune hepatitis or other immune‐mediated diseases. This may impact safety and efficacy of interferon‐based therapy of chronic hepatitis C. We investigated the association between a positive test result for a variety of autoantibodies and the initiation and efficacy of therapy for chronic hepatitis C. We analysed an observational cohort of 24 306 patients for an association between autoantibodies and treatment outcome. 8241 patients were tested simultaneously for antinuclear antibodies (ANA), liver kidney microsomal antibodies (LKM), smooth muscle antibodies (SMA) and antimitochondrial antibodies (AMA). Matched‐pair analysis was performed matching one autoantibody‐positive patient to three controls. Control patients had negative tests for all four antibodies. Analyses were performed for patients with a single positive autoantibody test and for patients with multiple positive autoantibody tests. A positive test result for ANA, LKM, SMA or AMA did not affect the physician's decision to initiate therapy with pegylated interferon and ribavirin. In addition, a positive test for one or multiple autoantibodies did not adversely affect sustained virologic response. There was no difference in fibrosis stage or alanine transaminase at baseline or during therapy irrespective of antibody status. Thyroid dysfunction was more frequent in patients with positive LKM antibodies (P = 0.004). Initiation of therapy for chronic hepatitis C and outcome were not affected by the presence of ANA, LKM, SMA or AMA. Routine testing of these autoantibodies seems not warranted. Determination of autoantibodies should be guided by individualized clinical decisions.