摘要
目的分析抗可溶性肝抗原(抗-SLA)抗体阳性肝病患者的特征及临床意义。方法收集2010年1月至2018年12月于北京佑安医院就医的77例抗-SLA阳性患者血清,免疫印迹法检测抗-SLA、抗肝细胞溶质Ⅰ型抗体(抗-LC1)、抗糖蛋白210抗体(抗-gp210)和抗核蛋白体100抗体(抗-sp100);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)、抗肝肾微粒体抗体(抗-LKM)等自身抗体。采用单因素方差分析比较抗-SLA不同强度组间的年龄;采用非参数秩和检验比较抗-SLA不同强度组的肝功能指标和免疫球蛋白,P<0.05为差异有统计学意义,多组间进一步作两两比较,对检验水准(α=0.05)进行校正后α'=0.0083,P<0.0083为差异有统计学意义。结果77例抗-SLA阳性者平均年龄(52.50±1.25)岁,女性70例(90.9%),男性7例(9.1%)。抗-SLA阳性者80.5%(62/77)初诊时抗体即强阳性(+++^++++)。抗SLA++组的丙氨酸氨基转移酶(ALT)水平高于抗SLA++++组(232.7 U/L比65.6 U/L,χ^2=7.751,P=0.005),抗SLA+++组的免疫球蛋白M(IgM)水平低于抗SLA++++组(1270 mg/L比2270 mg/L,χ^2=8.337,P=0.004);抗-SLA不同强度组间的年龄、其他肝功能和免疫学指标之间未见统计学差异。抗-SLA与ANA共阳性70例(90.9%)、与SMA共阳性13例(16.9%)、与抗-LKM和抗-LC1无共阳性者。抗-SLA阳性者诊断自身免疫性肝炎(AIH)58例、自身免疫性肝炎/原发性胆汁性胆管炎重叠综合征(AIH/PBC OS)12例、药物性肝损伤2例、慢性乙型肝炎2例、甲型肝炎、戊型肝炎和艾滋病伴肝损伤各1例。AIH和AIH/PBC OS的病例占抗-SLA阳性者的90.9%(70/77),另7例诊断非AIH(及OS)的患者中5例均有IgG水平升高,表现出AIH的特征。抗-SLA与AMA(中高滴度)共阳性者12例诊断为AIH/PBC OS。抗-SLA阳性者中已进入肝病晚期或终末期患者36.4%(28/77),包括肝硬化失代偿期22例、慢加急性肝衰竭4例、肝移植1例及肝衰竭死亡1例。结论抗-SLA对AIH具有高度诊断特异性,在PBC患者中抗-SLA阳性应作为诊断AIH/PBC重叠综合征的重要依据。
Objective To understand the characteristics and clinical significance of anti-soluble liver antigen antibody(anti-SLA)in patients with liver diseases.Methods Serum samples from seventy-seven patients with anti-SLA were collected from Beijing You'An Hospital during the period between January 2010 and December 2018.Anti-SLA,anti-liver cytosol type 1 antibody(anti-LC1),anti-glycoprotein 210 antibody(anti-gp210)and anti-nuclear body protein sp100 antibody(anti-sp100)were detected by immunoblotting;indirect immunofluorescence assay used for detecting anti-nuclear antibody(ANA),anti-mitochondrial antibody(AMA),anti-smooth muscle antibody(SMA),and anti-liver kidney microsome antibody(anti-LKM).One-way analysis of variance was used to compare the ages of different anti-SLA groups.The non-parametric rank sum test was used to compare the liver function indexes and immunoglobulins in different intensity groups of anti-SLA.P<0.05 was considered statistically significant.Further comparisons were made between the two groups,the correction levelα′=0.0083,P<0.0083 was considered statistically significant.Results The average age of 77 anti-SLA positive patients was(52.50±1.25)years old,70 females(90.9%)and 7 males(9.1%).80.5%of anti-SLA-positive patients(62/77 cases)were strongly positive at the time of initial diagnosis(+++to++++).The Alanine aminotransferase(ALT)level in the SLA++group was higher than that in the SLA++++group(232.7 U/L vs 65.6 U/L,χ^2=7.751,P=0.005)and the immunoglobulin M(IgM)level in the SLA+++group was lower than that in the SLA++++group(1270 mg/L vs 2270 mg/L,χ^2=8.337,P=0.004).There was no significant difference in age,other liver function and immunological indicators among the different groups.Seventy cases(90.9%)were both anti-SLA and ANA positive,13 cases(16.9%)were positive with SMA,and none positive with anti-LKM and anti-LC1.Among anti-SLA positive patients,58 cases were diagnosed with autoimmune hepatitis(AIH),12 were AIH/primary biliary cholangitis(PBC)overlap syndrome(OS),2 were drug-induced liver injury,2 were chronic hepatitis B,and 3 were hepatitis A,hepatitis E and acquired immune deficiency syndrome(AIDS)with liver injury,respectively.Cases of AIH and AIH/PBC OS accounted for 90.9%(70/77 cases)of anti-SLA-positive patients,and 5 of 7 patients diagnosed with non-AIH(and OS)had elevated IgG,showing AIH feature.92.3%(12/13 cases)of anti-SLA with high titers of AMA were diagnosed as AIH/PBC overlap syndrome.Of the 77 anti-SLA-positive patients,28(36.4%)had advanced or end-stage liver disease,including decompensated cirrhosis(22 cases),chronic acute liver failure(4 cases),and liver transplantation(1 case)and death from liver failure(1 case).Conclusions Anti-SLA has high diagnostic specificity for AIH;anti-SLA positive in patients with PBC should be an important biomarker for the diagnosis of AIH/PBC overlap syndrome.
作者
张海萍
马胤雪
李丽娟
赵丹彤
陈欣欣
娄金丽
闫惠平
Zhang Haiping;Ma Yinxue;Li Lijuan;Zhao Dantong;Chen Xinxin;Lou Jinli;Yan Huiping(Center of Clinical Laboratory,Clinical Research Center for Autoimmune Liver Disease,Beijing You′An Hospital,Capital Medical University,Beijing 100069,China)
出处
《中华检验医学杂志》
CAS
CSCD
北大核心
2019年第11期927-932,共6页
Chinese Journal of Laboratory Medicine
基金
北京市自然科学基金(7111004)
首都医学发展科研基金(2011-2018-05)。
关键词
肝疾病
肝炎
自身免疫性
自身抗体
Liver diseases
Hepatitis,autoimmune
Autoantibodies
