抗双链DNA抗体阳性肝功能异常患者临床及生化特征

抗双链DNA抗体（antibodies to double stranded DNA，anti—dsDNA）是系统性红斑狼疮的标志性抗体。但随着自身抗体检测的普及和检测水平的不断提高，在其他自身免疫性疾病中也可检出anti—dsDNA，为探讨anti-dsDNA在肝功异常患中检出情况及这部分患的临床及生化特征，我们收集2005年7月-2006年7月间884例肝功异常患的血清进行anti-dsDNA检测，现将结果报道如下。[第一段]     

抗核小体抗体、抗双链DNA抗体和抗超敏双链DNA抗体与系统性红斑狼疮的相关性研究

目的 通过检测系统性红斑狼疮(SLE)患者血清中抗核小体抗体(AnuA)、抗双链DNA (dsDNA)抗体和抗超敏双链DNA (dsDNA-NcX)抗体的水平,分析其在SLE患者中的敏感性、特异性及与其他实验室指标的相关性.方法 采用酶联免疫吸附试验(ELISA)法分别检测91例SLE患者、45例非SLE疾病对照和46例健康对照组血清中AnuA、抗dsDNA抗体和抗dsDNA-NcX抗体的水平,比较3种抗体对SLE诊断的敏感性和特异性,评价其与其他实验室指标的关系.结果 SLE患者AnuA、抗dsDNA抗体和抗dsDNA-NcX抗体的阳性率分别为49.45％、56.04％和61.54％;特异性分别为94.51％、94.51％和100.00％.AnuA、抗dsDNA抗体和抗dsDNA-NcX抗体均与SLEDAI评分呈正相关(r=0.50,P=0.00;r =0.49,P=0.00;r =0.42,P=0.00).ANA的滴度与AnuA的浓度呈正相关(r=0.30,P=0.00),与抗dsDNA抗体的滴度无相关性(r=0.19,P=0.08),与抗dsDNA-NcX抗体的浓度呈正相关(r=0.50,P=0.00).红细胞沉降率在抗dsDNA-NcX抗体、抗dsDNA抗体阴性和阳性组间比较差异无统计学意义(x2=0.76,P=0.38;x2=0.13,P=0.18),而在AnuA阴性与阳性组间比较差异有统计学意义(x2 =20.31,P=0.00).CRP及24小时尿蛋白定量在三者阴性与阳性组间比较差异无统计学意义.补体C3、C4在AnuA、抗dsDNA抗体和抗dsDNA-NcX抗体的阴性与阳性组间比较差异有统计学意义(x2=9.84,P=0.00;x2=16.53,P=0.00;x2 =10.33,P=0.00;x2 =11.61,P=0.00;x2 =12.69,P=0.00;x2=8.77,P=0.00).胱抑素在抗dsDNA抗体和AnuA的阴性与阳性组间比较差异无统计学意义,而在抗dsDNA-NcX抗体阴性与阳性组间比较差异有统计学意义(x2 =4.04,P=0.04).结论 抗dsDNA-NcX抗体可作为SLE的特异性抗体之一,其敏感性和特异性均高于抗dsDNA抗体和AnuA,三者均与SLE的疾病活动相关,联合检测有助于评估病情.     

抗核抗体、抗双链DNA抗体研究与实验室检测的进展

随着自身免疫性疾病（autoimmune diseases，AID）研究的深入，自身抗体愈来愈受到临床的重视。出现了以自身抗体命名的疾病，如抗磷脂综合征、抗Jo21综合征，还出现了以自身抗体作为诊断标准和分型依据的疾病，如自身免疫性肝炎、原发性胆汁性肝硬化。这些自身抗体在AID中研究，均极大地加速了AID的诊疗进程。随着循证医学的发展，AID的实验室检查，     

抗线粒体抗体阳性自身免疫性肝炎肝硬化一例

临床资料 患者,女性,55岁.因皮肤瘙痒3年,面部皮疹2年,肝硬化1年入院.患者3年前无明显诱因出现轻度皮肤瘙痒,以颜面部及上肢为主,未曾就诊.2年前发现上肢、颈面部散在毛细血管扩张,偶有上肢大关节肿痛,但无发热.     

放射免疫分析法测定抗双链DNA抗体在系统性红斑狼疮诊断中的应用

目的 探讨放免分析(RIA)法测定抗ds-DNA在系统性红斑狼疮(SLE)中的应用及临床意义.方法 分别用RIA法和间接免疫荧光法检测SLE活动期、缓解期患者及对照者血清中抗ds-DNA、ANA的水平并分析它们之间的关系.结果 在SLE活动期RIA法测定的抗ds-DNA水平较对照者显著增高(P<0.01),其阳性率为94%,间接免疫荧光法测定抗ds-DNA、ANA阳性率分别为62%、98%;在SLE缓解期三者阳性率分别为35.6%、30%、94%.结论 放免法测定抗ds-DNA提高了诊断的敏感性,对SLE的诊断和治疗有重要意义.     

肝病患者血清抗线粒体抗体的检测及其临床意义

自身免疫在不同肝病中的作用日益受到重视,抗线粒体抗体(antimitochon-drial antibody,AMA)作为一种自身抗体,在不同肝病中的检出情况鲜有报道。我们用ELISA法检测了96例不同肝病患者血清中的AMA,以探讨不同肝病检出AMA的差异以及AMA在肝病诊断中的意义。     

老年自身免疫性肝炎患者的临床特征及自身抗体水平

目的探讨老年自身免疫性肝炎(AIH)患者的临床特征及自身抗体水平。方法回顾性分析2013年1月至2018年1月期间首都医科大学附属北京佑安医院肝病免疫科收治的112例AIH患者的临床资料,按年龄分为老年组(≥60岁,33例)和中青年组(60岁,79例)。统计分析2组患者临床资料、生化指标和自身抗体指标。采用SPSS 16.0软件进行数据处理,根据数据类型,组间比较分别采用t检验、Mann-Whitney检验或χ~2检验。结果老年组患者乏力(54.5%vs78.5%)和恶心呕吐(18.2%vs 39.2%)症状患者显著少于中青年组,肝硬化(36.4%vs 17.7%)及合并肝外自身免疫病(33.3%vs 16.5%)患者显著多于中青年组,老年患者血小板计数[(155.2±76.1)×109/L vs (186.2±77.2)×109/L]显著低于中青年组,血尿素氮[(5.1±1.6) vs (4.4±1.3)mmol/L]及血肌酐[(62.1±16.2) vs (57.5±15.1)μmol/L]浓度显著高于中青年组,差异均有统计学意义(P0.05)。老年组抗核抗体阳性率高于中青年组(87.9%vs 79.7%),但差异无统计学意义(P0.05)。结论老年组AIH患者合并肝硬化、肝外免疫病的比例高,肾功能降低,年龄相关的免疫功能紊乱可能影响患者的临床表现。     

抗核抗体阳性肝硬化患者的临床特点

为了探讨抗核抗体 (ANA)阳性肝硬化患者的临床特点及环磷酰胺的治疗效果 ,检测 82例肝硬化患者血清ANA ,比较ANA阴性和阳性肝硬化患者的临床特点 ,观察环磷酰胺治疗ANA阳性肝硬化患者的疗效。结果与ANA阴性肝硬化患者比较 ,ANA阳性肝硬化患者女性多见 ,发病年龄较大 ,乙型肝炎病毒感染率低 ,Child -Pugh分级C级比例高 ;腹水、下肢浮肿症状较重 ;血清白蛋白水平低、球蛋白水平高 (P <0 0 5 )。ANA阳性肝硬化患者经环磷酰胺治疗后症状均好转 ,其中与对照组比较 ,腹水、下肢浮肿症状改善明显 (P <0 0 5 ) ;血清总蛋白、白蛋白水平增加 ,球蛋白水平下降 (P <0 0 5 ) ;部分患者ANA转阴 (P <0 0 5 )。说明ANA阳性肝硬化患者有其自身的临床特点 ,环磷酰胺治疗有效。     

α-辅肌动蛋白在IgG型抗双链DNA抗体与系膜细胞结合中的作用

目的探讨α-辅肌动蛋白在介导IgG型抗双链DNA(dsDNA)抗体与系膜细胞结合过程中的作用。方法将体外培养的大鼠系膜细胞株分成4组,其中3组分别与含有IgG型及IgM型抗dsDNA抗体(Ⅰ组)、含IgM型抗dsDNA抗体(Ⅱ组)以及正常(Ⅲ组)的大鼠血清共同孵育;Ⅳ组预加兔抗鼠α-辅肌动蛋白单抗[并分出少许细胞与辣根过氧化物酶(HRP)-羊抗兔lgG孵育,二氨基联苯胺(DAB)显色],然后与Ⅰ组同样的血清进行孵育。4组都加入异硫氰酸荧光素(FJTC)标记羊抗大鼠IgG单抗,采用流式细胞仪测定细胞表面荧光指数值,同时检测各组系膜细胞的增殖率与活细胞比例。结果从Ⅳ组分出并与HRP-羊抗兔IgG孵育的系膜细胞经DAB显色呈阳性;Ⅰ-Ⅳ组系膜细胞的表面荧光指数分别为1.59±O.22、0.65±0.17、0.66±0.18及0.72±0.16,其中Ⅰ组较Ⅱ～Ⅳ组高(P<0.05),而各组细胞的增殖水平与活细胞比例差异无统计学意义(P>0.05)。结论IgG型抗dsDNA抗体可能通过α-辅肌动蛋白与系膜细胞发生交叉结合反应。     

187例自身免疫性肝病的临床特点分析

目的分析自身免疫性肝病（AILD）的临床、生化及免疫学特点。方法分析北京大学人民医院2001年1月～2010年12月187例自身免疫性肝病患者的临床表现、生化及免疫学特点。结果 AILD的发病以40岁以上女性多见,30.5%（57/187）的患者确诊时已进展为肝硬化失代偿期。临床症状无特异性,自身免疫性肝炎（AIH）以ALT、IgG及γ球蛋白升高更为明显（P〈0.05）,而PBC以ALP、GGT、IgM升高更为明显（P〈0.05）。AILD患者常合并一种或多种肝外自身免疫病,AILD合并干燥综合症最为常见,AIH组及PBC组合并干燥综合症的发生率均达30%以上。AILD患者均有一种或多种自身抗体阳性,其中AIH组ANA阳性率为88.3%,AMA阳性率为7.5%（3/40）,AMA-M2阳性3.7%（2/54）;PBC组ANA阳性率为88.2%（97/110）,AMA阳性率为96.4%（81/84）,AMA-M2阳性率为94.4%（85/90）。AIH患者主要应用糖皮质激素治疗,其中共46例（59.7%）患者单用或联用UDCA治疗后肝脏酶学指标改善。结论生化、免疫学、自身抗体等检查对诊断与鉴别诊断具有重要意义。UDCA在AIH的治疗中有一定的作用。     

Prognostic implications of antibodies to Ro/SSA and soluble liver antigen in type 1 autoimmune hepatitis

Background: Antibodies to soluble liver antigen are frequently co‐expressed with antibodies to ribonucleoprotein/Sjögren's syndrome A (Ro/SSA) in autoimmune hepatitis. Aims: Our goals were to evaluate the prognostic implications of antibodies to Ro/SSA in type 1 autoimmune hepatitis and to determine their independence from antibodies to soluble liver antigen. Methods: Three hundred and seventy‐six serum samples from 170 patients were tested by enzyme immunoassays. Results: Sixty‐five patients (38%) had antibodies to Ro52; 11 patients (6%) had antibodies to Ro60; and 27 patients had antibodies to soluble liver antigen (16%). Twenty‐six patients with antibodies to Ro52 had antibodies to soluble liver antigen (40%), and 26 patients with antibodies to soluble liver antigen had antibodies to Ro52 (96%). Patients with antibodies to Ro52 and antibodies to soluble liver antigen had a higher frequency of human leucocyte antigen (HLA) DRB1^*03 (78 vs 50%, P=0.05) and lower occurrence of HLA DRB1^*04 (22 vs 57%, P=0.01) than patients with antibodies to Ro52 alone. Antibodies to Ro52 alone [hazard ratio (HR), 2.90; 95% confidence interval (CI), 1.18–7.14, P=0.02] and antibodies to Ro52 in conjunction with antibodies to soluble liver antigen (HR, 2.98; 95% CI, 1.07–8.43, P=0.04) were independently associated with the development of cirrhosis and hepatic death or liver transplantation. Conclusions: Antibodies to Ro52 alone and antibodies to Ro52 in conjunction with antibodies to soluble liver antigen are independently associated with a poor prognosis in type 1 autoimmune hepatitis. The prognostic implications ascribed to antibodies to soluble liver antigen may reflect their almost invariable concurrence with antibodies to Ro52.     

Detection of anti-double and anti-single stranded DNA antibodies in chronic liver disease: Significance of anti-double stranded DNA antibody in autoimmune hepatitis

Anti-DNA antibodies were determined by an enzyme-linked immunosorbent assay in 116 patients with chronic liver disease consisting of 21 cases of autoimmune hepatitis (AIH), 17 of primary biliary cirrhosis (PBC), and 78 of non-autoimmune-type of chronic liver disease. The assay was also performed on 83 patients with collagen disease, as a control group. Anti-double stranded DNA antibody (anti-dsDNA) was detected in 10/21 (48%) of the AIH patients and in 3/17 (17%) of the PBC patients, but not in those with other liver diseases. In contrast, anti-single stranded DNA antibody (anti-ssDNA) was positive not only in AIH and PBC, but also in those with non-autoimmune-types of chronic liver disease. Follow-up liver histology disclosed that the 2 patients with AIH who were positive for anti-dsDNA developed liver cirrhosis, whereas the 4 patients who were negative for anti-dsDNA, and those who showed a disappearance of anti-dsDNA following corticosteroid therapy, improved from chronic active to chronic persistent hepatitis.     

自身免疫性肝炎治疗应答速度与疾病进展的相关性

目的评价自身免疫性肝炎(AIH)患者治疗应答速度与肝硬化进展的关系,分析影响应答速度的因素。方法回顾性分析2001年11月-2017年5月在天津医科大学总医院就诊的61例长期随访的AIH患者的临床资料,依据血清转氨酶应答速度(即转氨酶降至正常水平所需时间)分为<3个月组、3~6个月组、6~12个月组、12~24个月组、>24个月组。比较各组的持续应答率及肝硬化进展率,并分析影响应答速度的因素。正态分布的计量资料2组比较采用两独立样本t检验,多组比较采用单因素方差分析。计数资料2组比较采用χ2检验,多组比较采用列联表卡方检验。结果转氨酶在3个月内降至正常的患者发生肝硬化的比例(20%)最低,肝功能持续2年未降至正常的2例患者全部进展为肝硬化,肝功能持续1年未降至正常的患者有一半以上(62.5%)进展为肝硬化。比较3个月内应答者与3个月内未应答者肝硬化的进展率(20%vs 48.15%),发现早期应答较晚期应答者肝硬化进展的比例低,差异有统计学意义(χ2=5.067,P<0.05)。将3个月内应答组(20%)分别与3~6个月应答(41.7%)、6~12个月应答(20%)、12~24个月应答(62.5%)以及>24个月应答组(100%)比较,发现3个月内应答组较12~24个月、>24个月应答组肝硬化的进展率低,差异均有统计学意义(χ2值分别为5.546、6.400,P值均<0.05)。并且3个月内应答组较12~24个月应答组发生持续转氨酶应答的比例高,差异有统计学意义(χ2=4.322,P<0.05)。结论 AIH患者的治疗应答速度与预后有关,早期应答者肝硬化的进展率较低,3个月内应答可能是提示预后较好的一个早期的时间标准,而1年以上仍未应答可能是提示预后较差的一个晚期的时间标准。初始ALT水平及治疗药物可能会影响应答速度。     

自身免疫性肝炎和原发性胆汗性肝硬化患者检测可溶性细胞间黏附分子1的临床价值

目的：探讨原发性胆汁性肝硬化（PBC）和自身免疫性肝炎（AIH）患者中检测可溶性细胞间黏附分子1（sICAM-1）的临床价值。方法选择2012年6月-2013年9月住院及门诊就诊的PBC患者61例，其中初发患者29例，缓解期患者21例，复发患者11例；AIH患者共59例，其中初发患者26例，缓解期患者20例，复发患者13例。健康对照50例。血清sICAM-1测定方法为双抗体夹心酶联免疫吸附法，采用生物化学酶法测定血清ALT、TBil。各组间比较采用方差分析，相关性采用Pearson相关分析。结果 PBC患者中，初发组和复发组sICAM-1水平均明显高于缓解组和对照组（P均＝0．000）；初发组和复发组之间sICAM-1水平差异无统计学意义（P＝0．484）；缓解组sICAM-1水平高于对照组（P＝0．000）；AIH患者中，初发组和复发组sICAM-1水平均明显高于缓解组和对照组（P均＝0．000）；初发组和复发组之间sICAM-1水平差异无统计学意义（P＝0．802）；缓解组和对照组之间sICAM-1水平差异无统计学意义（P＝0．281）；PBC、AIH患者血清sICAM-1与ALT呈正相关（r＝0．664，P＝0．000；r＝0．784，P＝0．000）；PBC、AIH患者血清sICAM-1与TBil呈正相关（r＝0．715，P＝0．000；r＝0．580，P＝0．000）。结论 sICAM-1可能参与PBC、AIH的免疫损伤机制，PBC、AIH患者血清sICAM-1水平升高程度与肝损害严重程度有密切关系，临床上动态观察其血清水平的变化，可望在病情活动评估、判断预后、指导治疗中起重要作用。     

乙型肝炎相关性肝衰竭患者HBV DNA低水平复制及特异性抗体表达的临床意义

目的探讨乙型肝炎相关性肝衰竭患者血清HBV DNA低水平复制及HBV特异性抗体表达的相关因素及临床意义。方法收集2008年6月至2013年12月于天津市第二人民医院住院治疗的391例乙型肝炎相关性肝衰竭患者及394例慢性乙型肝炎患者的病历资料。比较乙型肝炎相关性肝衰竭与慢性乙型肝炎患者HBV DNA表达的不同及影响因素分析。根据HBV血清学标志物(HBV M)特异性表达的不同将肝衰竭患者分为特异性抗体阳性(指抗-HBs、抗-HBe和抗-HBc同时阳性)和特异性抗体阴性(无抗-HBs、抗-HBe和抗-HBc同时阳性)2组,分析2组患者HBV DNA水平的变化和生存情况。组间比较采用独立样本t检验或MannWhitney秩和检验,计数资料比较采用χ2检验。结果乙型肝炎相关性肝衰竭患者HBV DNA水平低于慢性乙型肝炎组,差异有统计学意义(Z=-16.469,P0.05);HBeAg阳性和阴性的肝衰竭患者HBV DNA水平均低于相应的慢性乙型肝炎患者,差异有统计学意义(Z分别为-11.665和-12.853,P0.05)。在391肝衰竭病例中,HBV特异性抗体阳性组29例(7.42%),死亡25例(86.21%),HBV特异性抗体阴性组362例(92.58%),死亡157例(43.37%),2组病死率差异有统计学意义(P0.05)。特异性抗体阳性组患者HBV DNA水平明显低于特异性抗体阴性组,差异有统计学意义(Z=-3.594,P0.05)。2组HBeAg阴性患者HBV DNA水平均低于HBeAg阳性患者,差异有统计学意义(Z分别为7.427和7.513,P0.05)。结论 HBV M表达形式及机体免疫状态的动态变化在乙型肝炎相关性肝衰竭的发生发展过程中起着一定作用,HBV DNA低水平复制系机体处于免疫清除期所致,而同时伴抗-HBs、抗-HBe、抗-HBc 3个抗体同时阳性则提示机体对HBV的超强免疫反应,致使病情恶化、发展迅速,病死率高。     

Peripheral blood lymphocytes DNA in patients with chronic liver diseases

BACKGROUND: Viral replication in blood cells with nucleases may lead to the damage of lymphocytes genetic apparatus and the beginning of immunopathological reactions. AIM: Of this investigation is to reveal the damage to peripheral blood lymphocytes (PBL) DNA in the patients with chronic liver diseases. MATERIALS AND METHODS: Sixteen-nine patients with chronic liver diseases (37 patients with chronic viral hepatitis, 2 patients with liver cirrhosis of mixed etiology (alcohol+virus G), 30 women with primary biliary cirrhosis-PBC) were examined. The condition of DNA structure of PBL was measured by the fluorescence analysis of DNA unwinding (FADU) technique with modification. Changes of fluorescence (in %) reflected the DNA distractions degree (the presence of DNA single-stranded breaks and alkalinelabile sights). RESULTS AND CONCLUSION: The quantity of DNA single-stranded breaks and alkalinelabile sights in DNA in all patients with chronic viral hepatitis didn't differ from the control group, excluding the patients with chronic hepatitis (CH) C+G. Patients with HGV and TTV monoinfection had demonstrated the increase of the DNA single-stranded breaks PBL quantity. This fact may be connected with hypothesis about the viruses replication in white blood cells discussed in the literature. Tendency to increase quantity of DNA PBL damages in the patients with primary biliary cirrhosis (PBC) accordingly to the alkaline phosphatase activity increase was revealed. Significant decrease of the DNA single-stranded breaks and alkalinelabile sights in the PBC patients that were treated with prednisone was demonstrated. Probably, the tendency to increase the quantity of DNA single stranded breaks and alkalinelabile sights in lymphocytes of the PBC patients was depended on the surplus of the blood bile acid content.     

自身免疫性肝炎后肝硬化合并原发性免疫性血小板减少1例报告

自身免疫性肝炎(AIH)是一种由针对肝细胞自身免疫反应所介导的肝脏实质炎症[1]。AIH常合并其他器官或系统性自身免疫性疾病如:桥本氏甲状腺炎(10%~23%)、糖尿病(7%~9%)、炎症性肠病(2%~8%)、类风湿性关节炎(2%~5%)、干燥综合征(1%~4%)、银屑病(3%)和系统性红斑狼疮(1%~2%)等[2]。而合并原发性免疫性血小板减少(primary immune thrombocytopenia,IPT)者少见,国内外均罕见报道。     

自身免疫性肝病重叠综合征的临床治疗探讨

目的探讨自身免疫性肝病重叠综合征的治疗方法,提高治疗的有效性与安全性。方法 32例自身免疫性肝炎（AIH）-原发性胆汁性肝硬化（PBC）重叠综合征患者,均给予强的松（0.5mg.kg-1.d-1）联合熊去氧胆酸（UDCA,15 mg.kg-1.d-1）治疗,回顾性分析治疗前、后不同时段患者疾病状态的变化,评价临床疗效。结果所有患者症状、体征明显减轻,生化指标、肝脏病理损害均明显改善,与入院前比较差异有统计学意义（P〈0.01或P〈0.05）。IgG、IgM、抗平滑肌抗体（SMA）、抗线粒体抗体（AMA）治疗前后无明显变化,差异无统计学意义（P〉0.05）。结论强的松联合UDCA短期内能明显减轻AIH-PBC患者的临床症状、体征,改善生化学和肝组织学指标,提高患者生存质量,治疗安全有效。     

Profiles of antinuclear antibodies in chronic active hepatitis,primary biliary cirrhosis and alcoholic liver disease

ABSTRACT— The profiles of specific antinuclear antibodies were determined in sera from 23 patients with the idiopathic type of chronic active hepatitis (CAH), 15 patients with primary biliary cirrhosis (PBC) and 25 patients with alcoholic liver disease (ALD). The indirect immunofluorescence test for antinuclear antibodies using cultured human embryonic fibroblasts as substrate was positive in 78% in CAH, in 73% in PBC and in 24% in ALD. Seventeen percent of CAH sera and 33% of PBC sera stained small speckles in interphase nuclei. This staining pattern probably represents a new subset of ANA as the centromeres (kinetochores) were not stained. Antibodies to native DNA by the Crithidia luciliae test were found in only one serum from a patient with CAH. In addition, 17 percent of the CAH sera reacted with the saline extract of rabbit thymus by double immunodiffusion. Antibodies to the Sm- or RNP-antigens were not found. SS-B antibodies could be demonstrated in 39% of the CAH sera by a sensitive immunoenzymatic technique. Patients with CAH also had significantly higher levels of antibodies against denatured, single-stranded DNA (ss-DNA) and a synthetic RNA molecule, poly(A) as compared to other groups. Patients with an atypical cholestatic CAH had an antinuclear-antibody profile resembling that of the other CAH patients, but different from that of PBC patients. Patients with alcoholic cirrhosis had significantly higher levels of ss-DNA- and poly(A)-antibodies than other patients with ALD. It is concluded that the determination of an antinuclear-antibody profile using the ELISA seems to be clinically useful in the classification of chronic liver diseases.