自身抗体在乙型病毒性肝炎和自身免疫性肝炎中的特点分析

Characteristics of autoantibodies in hepatitis B and autoimmune hepatitis

目的分析自身抗体在乙型病毒性肝炎及自身免疫性肝炎中的特点。方法将血清样本分为3组:乙型病毒性肝炎组(HBV)306例、自身免疫性肝炎组(AIH)235例和健康对照组150例,采用间接免疫荧光法和欧蒙印迹法检测血清中抗核抗体(ANA)、抗平滑肌抗体(ASMA)、抗线粒体抗体(AMA)、抗肝肾微粒体Ⅰ型(LKM-1)抗体和抗可溶性肝抗原/肝胰抗原(SLA/LP)抗体等肝病相关自身抗体。结果 (1)HBV组和AIH组ANA检出率分别为9.1%、80.42%,明显高于健康对照组;AIH组ANA阳性率显著高于HBV组(P<0.05)。(2)HBV组ANA滴度1∶100、1∶320、1∶1 000阳性率分别为6.2%、2.6%、0.3%,以低滴度(1∶100)为主,AIH组1∶100、1∶320、1∶1 000滴度阳性率分别为22.98%、41.28%、14.47%,以高滴度(≥1∶320)为主。(3)HBV组AMA、ASMA、抗LKM-1及抗SLA/LP抗体的阳性率分别是0.3%、0.9%、0.3%和0%,AIH组的阳性率分别为36.6%、25.1%、23%和2.55%,明显高于HBV组。(4)AIH组荧光模型以核均质型和核仁型为主;HBV患者以颗粒型为主。(5)采用1999年诊断积分系统评估,28例自身抗体阳性乙肝患者中有1例评分超过16分,达到自身免疫性肝炎确诊标准(≥16分)。结论自身免疫性肝炎患者具有高滴度的自身抗体;乙型病毒性肝炎患者血清中低滴度的自身抗体不构成自身免疫性肝炎,高滴度的自身抗体要结合临床资料排除自身免疫性肝炎。

Objective To characterize the autoantibody profiles in the patients with hepatitis B and those with autoimmune hepatitis. Methods The subjected patients who admitted in our institute from January 2014 to May 2015 were divided into 3 groups： hepatitis B virus group （HBV, n = 306） , autoimmune hepatitis group （AIH, n = 235）, and healthy control （n = 150）. Indirect immunofluorescence and EUROLINE assays were performed to detect a panel of autoantibodies, including anti-nuclear antibody （ ANA）, anti-small muscle antibody （ ASMA）, anti-mitochondrial antibody （ AMA, ） anti-liver kidney microsome type 1 （ LKM-1 ）, and anti-soluble liver antigen/liver pancreas （SLA/LP） in the sera. Results （ 1 ） The prevalence of ANA in HBV and AIH were 9. 1% and 80.42%, which was obviously higher than that in control. Moreover, the significant higher prevalence of ANA was seen in AIH than HBV （ P 〈 0.05 ）. （2） The positive rate of ANA with titers of 1： 100, 1： 320, and 1：1 000 in HBV were 6.2%, 2.6%, and 0.3%, respectively, indicating that positive rate of ANA was very low in HBV and mainly detectable in low （ 1 ： 100） titer. In contrast, ANA positivityin AIH with titers of 1： 100, 1：320, and 1：1 000 were 22.98%, 41.28%, and 14.47%,respectively. The positive ANA with titer 1 ： 320 in AIH was strikingly higher than in HBV. （3） Positive rates of AMA, ASMA, anti-LKM-1 and anti-SLA/LP antibodies in HBV （0.3%, 0.9%, 0.3%, and 0% ） were much lower than those in AIH （36. 6%, 25. 1%, 23%, and 2. 55%）. （4） The fluorescent staining displayed a majority of homogeneous and nucleolar type of ANA in AIH, whereas granular type was dominated in HBV. （5） Among 28 chronic HBV patients with positive autoantibodies, only one patient met the comprehensive criteria of International Autoimmune Hepatitis Group （IAIHG） in 1999 with an IAIHG score ≥16. Gonolusion Our data indicate that patients with HBV and AIH are both positive to autoantibodies, thus a low titer of autoantibody posifivity can not serve as diagnostic criterion for AIH. Positive high titer of autoantibodies combined with clinical manifestation is useful for differential diagnosis between these 2 diseases.