原发性胆汁性肝硬化患者的免疫学特点分析

Immunological characteristics of primary biliary cirrhosis patients

目的分析原发性胆汁性肝硬化(PBC)出现的自身抗体等免疫学指标及其临床意义.方法对3 000例肝功能异常患者采用间接免疫荧光法检测抗核抗体(ANA)、抗线粒体抗体(AMA)、抗平滑肌抗体(SMA)和抗肝肾微粒体抗体(抗LKM)等,并对ANA和AMA亚型及抗可溶性肝抗原/肝胰抗原(抗SLA/LP)、LKM 1和抗肝特异性胞浆抗原型1抗体(抗-LC-1)等肝脏疾病相关的自身抗体进行了检测.结果3000例肝病患者中,PBC 52例占1.7%.PBC患者的AMA和AMA-M2抗体均为阳性,52例PBC中,94.0%呈AMA高滴度(≥1:320)阳性,79.0%M2＞200 RU/L,78.0%ANA阳性.ANA的主要荧光模式为细胞核膜型、细胞核点型和着丝点型.少见的荧光模式有抗干燥综合征A/B(SS-A/SS B)、细胞核均质型、核仁型及颗粒型等.PBC患者免疫球蛋白M、碱性磷酸酶和γ-谷氨酰转肽酶高于乙型肝炎肝硬化患者;其白细胞介素(I L)6、IL-10、肿瘤坏死因子α和干扰素γ水平高于正常人.5例表现为自身免疫性肝病重叠综合征,其中2例抗-SLA/LP阳性,提示PBC与自身免疫性肝炎(AIH)3型的重叠;1例抗-LKM-1阳性,提示PBC与AIH 2型的重叠;2例ANA阳性,且肝活体组织检查证实存在AIH和PBC的病理改变,提示为PBC与AIH 1型的重叠综合征.结论 PBC在我国肝病患者中约占1%～2%.临床已出现典型症状者一般均有高水平AMA和M 2抗体,多数患者ANA阳性,并有较典型的荧光模式.细胞因子水平升高,提示体液免疫和细胞免疫的异常可能与发病机制相关.

Objective To study the clinical significance of the immunological characteristics in patients with primary biliary cirrhosis (PBC). Methods 3000 patients with abnormal liver functions were examined for anti-nuclear antibodies (ANA), anti-mitochondral antibodies (AMA), anti-smooth muscle antibodies (SMA) and anti-liver kidney microsomal antibody (LKM) using immunofluorescent assays (IFA). LKM-1, liver cytosolic-1 (LC-1), soluble liver antigen (SLA)/liver- pancreas antigen (LP) and subtype of AMA (M2, M4, M9) as well as ANA profile were detected by an immune blotting assay and an enzyme-linked immune absorbent assay (ELISA), respectively. Cytokines were tested by flow cytometry. Results Of the 3000 patients with liver diseases, 52 (1.7%) were diagnosed with PBC. All the PBC cases were positive for AMA and M2. 94% of them showed high liter of AMA (≥ 1 : 320), and in 79% of them M2 was >200 RU/L, and 78% of them were ANA positive. Three main fluorescent patterns of ANA seen were nuclear membrane, nuclear dots and centromere patterns. Sjogren's Syndrome A/B (SS-A/B), homogenous, nucleolar or nuclear granular patterns were seen in only a few patients. IgM, ALP and GGT in PBC patients were significantly higher than those in hepatitis B related liver cirrhosis patients. The levels of IL-6, IL-10, TNF-α and IFN-γ in PBC patients were higherthan in the normal controls. Among the 52 PBC patients, 5 had autoimmune liver disease overlap syndromes. Two of them were SLA/LP positive, indicated as AIH type Ⅲ and PBC overlapping, and 1 was LKM-1 positive showing AIH type Ⅱ overlapping PBC, and 2 had ANA positive and were identified as AIH and PBC by liver biopsy. Conclusion The percentage of PBC in Chinese liver disease patients is about 1%-2%. Most of the PBC patients have high levels of AMA and AMA-M2, IgM, ALP, GGT and several cytokines, indicating that abnormality of humeral and cellular immunity may be associated with the pathogenisis of PBC.