Swanson N R, Reed W D, Yarred L J, Shilkin K B, Joske R A
Department of Medicine, University of Western Australia, Nedlands.
Hepatology. 1990 Apr;11(4):613-21. doi: 10.1002/hep.1840110414.
The fine specificity of autoantibodies to human hepatocyte plasma membranes in autoimmune chronic active hepatitis was determined by one-dimensional immunoblotting. Sera from 12 patients with "classical" autoimmune chronic active hepatitis contained autoantibodies recognizing many human hepatocyte plasma membrane polypeptides in the 15 to 220 kD range. Many of these autoantibodies titrated beyond 1:80,000 and some may be potentially "pathological." In particular, one band with an apparent molecular weight of 60 kD was a dominant and consistent finding in all patients with autoimmune chronic active hepatitis by immunoblotting. Serum absorption studies showed this band to be predominantly liver-specific. Control sera from patients with chronic persistent hepatitis, nonhepatic autoimmune disease and normal healthy subjects possessed low titer reactivity that most likely represented "natural" autoantibodies. Anti-human hepatocyte plasma membranes in autoimmune chronic active hepatitis consisted of all three immunoglobulin isotypes (G,M and A) and their presence was not caused by nonspecific reactions as a consequence of hypergammaglobulinemia. Autoantibodies were shown to be specific by virtue of their absorption and exhaustion on titration. Many were directed at species nonspecific determinants, however, some autoantibodies recognized human-specific polypeptides. The majority of anti-human hepatocyte plasma membranes appeared to be organ-specific as sera from patients with autoimmune chronic active hepatitis reacted only weakly with polypeptides of kidney plasma membranes. Of the activity detected, few bands corresponded with those obtained using polypeptides of human hepatocyte plasma membranes. Our results show that patients with autoimmune chronic active hepatitis possess an array of liver-specific autoantibodies to polypeptide subunits of human hepatocyte plasma membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
通过一维免疫印迹法测定了自身免疫性慢性活动性肝炎中针对人肝细胞质膜自身抗体的精细特异性。12例“典型”自身免疫性慢性活动性肝炎患者的血清中含有能识别15至220kD范围内多种人肝细胞质膜多肽的自身抗体。其中许多自身抗体的滴度超过1:80,000,有些可能具有潜在的“病理性”。特别是,一条表观分子量为60kD的条带在所有自身免疫性慢性活动性肝炎患者的免疫印迹中都是主要且一致的发现。血清吸收研究表明这条带主要是肝脏特异性的。慢性持续性肝炎患者、非肝脏自身免疫性疾病患者和正常健康受试者的对照血清具有低滴度反应性,很可能代表“天然”自身抗体。自身免疫性慢性活动性肝炎中的抗人肝细胞质膜由所有三种免疫球蛋白同种型(G、M和A)组成,它们的存在不是由高球蛋白血症导致的非特异性反应引起的。通过滴定吸收和耗竭证明自身抗体具有特异性。许多自身抗体针对的是物种非特异性决定簇,然而,一些自身抗体识别的是人类特异性多肽。大多数抗人肝细胞质膜似乎是器官特异性的,因为自身免疫性慢性活动性肝炎患者的血清与肾细胞质膜多肽的反应很弱。在检测到的活性中,很少有条带与用人肝细胞质膜多肽获得的条带相对应。我们的结果表明,自身免疫性慢性活动性肝炎患者拥有一系列针对人肝细胞质膜多肽亚基的肝脏特异性自身抗体。(摘要截短至250字)