Vergani D, Mieli-Vergani G, Mondelli M, Portmann B, Eddleston A L
Department of Immunology, King's College School of Medicine and Dentistry, London, U.K.
Liver. 1987 Dec;7(6):307-15. doi: 10.1111/j.1600-0676.1987.tb00361.x.
Hepatocytes isolated from patients with chronic liver disease are often covered by immunoglobulin. The aim of the present study was to establish whether this surface immunoglobulin (SIg) mediates liver cell damage. Freshly isolated hepatocytes from percutaneous liver biopsy of 16 patients with chronic active hepatitis (CAH) (6 HBsAg positive), 3 with HBsAg-positive chronic lobular hepatitis (CLH), 5 with HBsAg-positive chronic persistent hepatitis (CPH) and 12 with minor histological abnormalities (MHA) (5 HBsAg positive) were divided into two aliquots. One was studied for the presence of membrane-bound immunoglobulin and the third component of complement by direct immunofluorescence and the other was incubated, in an allogeneic cytotoxic assay, with peripheral blood mononuclear cells prepared from healthy volunteers as a source of effectors for antibody-dependent cell-mediated cytotoxicity (ADCC). Liver biopsies were scored for portal and parenchymal inflammatory activity. The percentage of SIg positive hepatocytes was significantly higher in patients with CAH (median 52.5%) than in patients with CLH/CPH (20.5%) or in patients with MHA (1%). Percentages of SIg-positive liver cells were significantly correlated with total liver biopsy scores and with both portal or parenchymal scores considered independently. SIg were found to belong to the IgG class in all groups of patients. When hepatocytes were cultured with normal human lymphocytes, allogeneic cytotoxicity values were significantly higher in patients with CAH (median 34%) than in patients with CLH and CPH (18%) or in those with MHA (12%). Percentage cytotoxicity was positively correlated with total biopsy scores and with portal activity but not with parenchymal activity, suggesting that ADCC might play a damaging role mainly in the portal areas.(ABSTRACT TRUNCATED AT 250 WORDS)
从慢性肝病患者中分离出的肝细胞常被免疫球蛋白覆盖。本研究的目的是确定这种表面免疫球蛋白(SIg)是否介导肝细胞损伤。从16例慢性活动性肝炎(CAH)(6例HBsAg阳性)、3例HBsAg阳性慢性小叶性肝炎(CLH)、5例HBsAg阳性慢性持续性肝炎(CPH)和12例轻微组织学异常(MHA)(5例HBsAg阳性)患者的经皮肝活检中新鲜分离出的肝细胞被分成两份。一份通过直接免疫荧光研究膜结合免疫球蛋白和补体第三成分的存在情况,另一份在同种异体细胞毒性试验中与从健康志愿者制备的外周血单个核细胞一起孵育,作为抗体依赖性细胞介导的细胞毒性(ADCC)效应细胞的来源。对肝活检进行门脉和实质炎症活动评分。CAH患者中SIg阳性肝细胞的百分比(中位数52.5%)显著高于CLH/CPH患者(20.5%)或MHA患者(1%)。SIg阳性肝细胞的百分比与肝活检总分以及单独考虑的门脉或实质评分显著相关。在所有患者组中,SIg均属于IgG类。当肝细胞与正常人淋巴细胞一起培养时,CAH患者的同种异体细胞毒性值(中位数34%)显著高于CLH和CPH患者(18%)或MHA患者(12%)。细胞毒性百分比与活检总分及门脉活动呈正相关,但与实质活动无关,这表明ADCC可能主要在门脉区域发挥损伤作用。(摘要截短于250词)