Klein R, Berg P A
Department of Internal Medicine, University of Tübingen, West Germany.
Hepatology. 1990 Aug;12(2):335-41. doi: 10.1002/hep.1840120222.
Sera from 81 healthy family members (including husbands) of 13 patients with primary biliary cirrhosis were tested by Western blotting against the antigen fractions M9 and M2 derived respectively from rat liver and beef heart mitochondria. Fifty-eight (70%) were positive and recognized four major (molecular weights 98 kD, 65 kD, 61 kD, 58 kD) and eight minor determinants (85 kD, 81 kD, 78 kD, 54 kD, 48 kD, 45 kD, 40 kD, 30 kD) labeled alpha-my. Each of the 58 sera recognized at least one of the four major polypeptides. In contrast, only 6% of 80 primary biliary cirrhosis patients had antibodies against one of these epitopes. Sera from 25 patients with different infectious disorders previously shown to react with submitochondrial particles by enzyme-linked immunosorbent assay also recognized at least one of the four major determinants. From these findings it was concluded that these antibodies may belong to the family of natural autoantibodies. Since they reacted with submitochondrial fractions, they were defined as "naturally occurring mitochondrial antibodies". The high incidence of "naturally occurring mitochondrial antibodies" in primary biliary cirrhosis-contact persons may be taken as indirect evidence for a contagious immunogenic agent circulating in the blood of primary biliary cirrhosis-patients. In contrast, the absence of "naturally occurring mitochondrial antibodies" in primary biliary cirrhosis-patients themselves implies that an underlying B-cell defect is responsible for this lack of antibody production. Considering the protective role of naturally occurring antibodies in general, this postulated B-cell defect could be a major factor in the etiopathogenesis of primary biliary cirrhosis.
采用蛋白质免疫印迹法，以分别来源于大鼠肝脏和牛心脏线粒体的抗原组分M9和M2，对13例原发性胆汁性肝硬化患者的81名健康家庭成员（包括丈夫）的血清进行检测。58人（70%）呈阳性，识别出4种主要（分子量98 kD、65 kD、61 kD、58 kD）和8种次要决定簇（85 kD、81 kD、78 kD、54 kD、48 kD、45 kD、40 kD、30 kD），标记为α-my。58份血清中的每一份都识别出4种主要多肽中的至少一种。相比之下，80例原发性胆汁性肝硬化患者中只有6%具有针对这些表位之一的抗体。25例先前经酶联免疫吸附测定显示与亚线粒体颗粒反应的不同感染性疾病患者的血清，也识别出4种主要决定簇中的至少一种。从这些发现得出结论，这些抗体可能属于天然自身抗体家族。由于它们与亚线粒体组分反应，因此被定义为“自然产生的线粒体抗体”。原发性胆汁性肝硬化接触者中“自然产生的线粒体抗体”的高发生率，可被视为原发性胆汁性肝硬化患者血液中循环存在传染性免疫原性因子的间接证据。相比之下，原发性胆汁性肝硬化患者自身缺乏“自然产生的线粒体抗体”，意味着潜在的B细胞缺陷是导致这种抗体产生缺乏的原因。考虑到天然抗体总体上的保护作用，这种假定的B细胞缺陷可能是原发性胆汁性肝硬化发病机制中的一个主要因素。
