原发性胆汁性肝硬化自身抗体特征及其对药物治疗的反应

Autoantibody Profile of Primary Biliary Cirrhosis and Treatment Response

目的研究原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)患者抗线粒体抗体(antimitochondrial antibody,AMA)、抗线粒体抗体M2亚型(AMA-M2)、抗GP210抗体和抗SP100抗体的临床相关性及对药物治疗的反应。方法82例初诊未治疗的PBC患者随机分为熊去氧胆酸(ursodeoxycholic acid,UDCA)(U组,28例)、UDCA联合泼尼松龙(UP组,27例)、UDCA联合硫唑嘌呤(azathioprine,AZP)(UA组,27例)3组,治疗前观察各组患者的AMA、AMA-M2、抗GP210抗体和抗SP100抗体,治疗后3、6个月复查AMA、AMA-M2。治疗前24例患者行肝穿刺检查获得标本,按组织学特点对其进行分期。结果PBC患者AMA滴度、AMA-M2水平与其临床症状、肝生化指标、肝脏病理改变无关,AMA与IgM呈正相关(P=0.046)。三种治疗方案对AMA、AMA-M2水平无影响。抗GP210抗体阳性患者比阴性患者病情重,治疗6个月时的肝脏生化指标缓解率低(P=0.012)。抗SP100抗体阳性与阴性PBC患者的临床症状、肝脏生化指标、IgM无差异。结论AMA、AMA-M2及抗SP100抗体对PBC患者有诊断意义,但其水平与病情无关,不受药物治疗影响,也不影响药物疗效。抗GP210抗体阳性PBC患者病情重,肝脏生化指标缓解率低。

Objective To investigate the autoantibody profile of primary biliary cirrhosis （PBC）, including anti-mitochondrial antibodies （AMA） and its subtype M2, anti-GP210 and anti-SP100, and their clinical relevance and treatment response. Methods Eighty-two untreated PBC patients were randomly allocated into three groups, including Group U （28 cases, treated with UDCA）, Group UP （27 cases, treated with UDCA plus prednisolone）, and Group UA （27 cases, treated with UDCA plus azathioprine）. AMA, AMA- M2, anti-GP210 and anti-SP100 were detected at baseline, and repeated to detect AMA, AMA-M2 after 3 and 6 months treatments. 24 liver biopsy specimens of patients were got at baseline, and were graded according to the histological features. Results The titers of AMA and AMA-M2 had no correlation with clinical manifestation, liver biochemical marks and .pathological changes, and did not change in either treatment arm. AMA positively correlated with IgM （P= 0.046）. PBC patients with anti-GP210 had a more severe disease course, but a less improvement of liver biochemical marks at 6 months of treatment than its counterpart （P= 0.012）. There is no difference of clinical manifestation, liver biochemical marks and IgM beween anti-SP100 positive and negative patients. Conclusion AMA, AMA-M2 and anti-SP100 have diagnostic values for PBC, though their levels are independent of treatment regimens and have no correlation with disease course. PBC patient with anti-GP210 has a more severe disease course.