多种自身抗体在原发性胆汁性胆管炎中的临床意义

Clinical significance of multiple autoantibodies in primary biliary cholangitis

目的探讨多种自身抗体在原发性胆汁性胆管炎(PBC)诊疗中的临床意义。方法收集58例原发性胆汁性胆管炎患者(PBC组)、60例病毒性肝炎患者(病毒性肝炎组)和60名健康体检者(正常对照组)。应用间接免疫荧光法分别检测抗核抗体(ANA)、抗线粒体抗体(AMA),用线性免疫印迹法分别检测抗线粒体2型抗体(AMA-M2)、抗gp210抗体(抗gp210)和抗sp100抗体(抗sp100),分析各种自身抗体单独检测及并联检测在PBC诊断中的意义。结果PBC组、病毒性肝炎组和正常对照组患者的ANA阳性率比较差异有统计学意义(P<0.05),其中PBC组的ANA阳性率最高、正常对照组的ANA阳性率最低,组间两两比较差异均有统计学意义(P均<0.017)。3组的ANA阳性者中,PBC组以中高滴度(1∶320及以上)为主,中高滴度者比例均高于病毒性肝炎组及正常对照组(P均<0.017),低滴度(1∶100)者比例低于病毒性肝炎组(P均<0.017)。PBC组54例ANA阳性患者中,ANA荧光核型以胞浆颗粒型(43%)与着丝点型(20%)为主。PBC组患者的ANA、AMA、AMA-M2、抗gp210、抗sp100及并联检测[ANA、AMA、AMA-M2、抗gp210抗体和(或)抗sp100抗体]的阳性率均高于病毒性肝炎组和正常对照组(P均<0.017),PBC组中并联检测的阳性率高于单独检测抗gp210和抗sp100(P均<0.05)。ANA(1∶320及以上)、AMA、AMA-M2、抗gp210和抗sp100以及并联检测在PBC患者中的灵敏度分别为88%、85%、78%、29%、16%和90%;特异度分别为92%、97%、98%、98%、100%和92%;阳性预测值分别为91%、96%、98%、94%、9/9和91%;阴性预测值分别为89%、87%、82%、59%、55%和90%。结论临床筛查PBC时,仅行ANA检测的患者出现中高滴度胞浆颗粒型结果时,应追加自身免疫肝抗体谱检测;并联检测自身抗体能够提高PBC的灵敏度,为临床提供更多诊断依据。

Objective To explore the clinical significance of multiple autoantibodies in the diagnosis and treatment of primary biliary cholangitis(PBC).Methods A total of 58 patients with PBC,60 patients with viral hepatitis,and 60 healthy people were recruited and assigned into three groups.The antinuclear antibody(ANA)and anti-mitochondrial antibody(AMA)were detected by indirect immunofluorescence assay(IIF).The anti-mitochondrial antibody M2 type(AMA-M2),anti-gp210 and anti-sp100 were determined by the linear immunoblotting(LIA).The significance of single and combined detection of different autoantibodies in diagnosis and treatment of PBC was evaluated.Results The positive rate of ANA significantly differed among the PBC,viral hepatitis and normal control groups(all P<0.05).The positive rate of ANA in the PBC group was the highest and that in the normal control group was the lowest.The positive rate of ANA significantly differed between any two groups(all P<0.017).For individuals with positive ANA,the proportion of patients with medium and high titer(1∶320 or above)in the PBC group was significantly higher compared with those in the viral hepatitis and normal control groups,respectively(both P<0.017),whereas the proportion of low titer(1∶100)was significantly lower than that in the viral hepatitis group(P<0.017).Among 54 patients with positive ANA in the PBC group,the ANA fluorescence karyotype mainly consisted of cytoplasmic and granule type(43%)and centromere type(20%).The positive rates of ANA,AMA,AMA-M2,anti-gp210 and antisp100 and combined detection of[ANA,AMA,AMA-M2,anti-gp210 and/or anti-sp100]in the PBC group were significantly higher compared with those in the normal control and viral hepatitis groups(all P<0.017).In the PBC group,the positive rate of combined detection of anti-gp210 and anti-sp100 was significantly higher than single detection of anti-gp210 and anti-sp100(both P<0.05).The sensitivity of ANA(1∶320 or above),AMA,AMA-M2,anti-gp210 and anti-sp100 and combined detection in the PBC patients was 88%,85%,78%,29%,16%and 90%,92%,97%,98%,100%and 92%for the specificity,91%,96%,98%,94%,9/9 and 91%for the positive predictive value,and 89%,87%,82%,59%,55%and 90%for the negative predictive value,respectively.Conclusions In the clinical screening of PBC,detection of liver autoantibody spectrum should be supplemented for patients presenting with medium and high titer of cytoplasmic granule type after receiving ANA detection alone.Combined detection of multiple autoantibodies can improve the detection rate of PBC,providing more diagnostic basis for clinical practice.