Kitami N, Ishii H, Shimizu H, Adachi H, Komada T, Mikami H, Yokoi Y, Sato N
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
J Gastroenterol Hepatol. 1994 Jan-Feb;9(1):7-12. doi: 10.1111/j.1440-1746.1994.tb01208.x.
Although antimitochondrial auto-antibodies are characteristically present in the serum of patients with primary biliary cirrhosis (PBC), there is a discrepancy between the positivity for antimitochondrial antibody (AMA) and that for anti-M2 auto-antibody. In an attempt to explain the discrepancy, this study investigates the relationship between the AMA titre, determined by indirect immunofluorescence, and immunoreactivity to four inner mitochondrial membrane proteins (M2 proteins) with molecular weights of 70, 50, 47, and 40 kDa in 129 patients with PBC. Antimitochondrial antibody positivity was identified in 114 (88%) of 129 patients with clinically and histologically confirmed PBC. There were no significant differences between the AMA-negative and AMA-positive groups in clinical characteristics or histologically determined disease stage. Immunoblot analysis showed that all patients had anti-M2 auto-antibodies to one or more of the four M2 proteins. Nine (60%) of the 15 AMA-negative patients had antibodies to only one M2 protein (either 70 or 47 kDa). In contrast, 34 (53%) of the 64 patients with high AMA titres (> or = 1:320) had antibodies to all four M2 proteins. There was a significant rank correlation between the AMA titre and the number of antibodies to M2 proteins (P < 0.01). These findings indicate that the AMA titre is not influenced by the immunogenicity of M2 proteins but by the number of M2 proteins that elicit an antibody response and that decreased immunoreactivity to M2 proteins may induce AMA negativity in PBC serum samples.
虽然抗线粒体自身抗体是原发性胆汁性肝硬化（PBC）患者血清中的特征性抗体，但抗线粒体抗体（AMA）阳性与抗M2自身抗体阳性之间存在差异。为了解释这种差异，本研究调查了129例PBC患者中，通过间接免疫荧光法测定的AMA滴度与对四种分子量分别为70、50、47和40 kDa的线粒体内膜蛋白（M2蛋白）的免疫反应性之间的关系。129例临床和组织学确诊为PBC的患者中，114例（88%）抗线粒体抗体呈阳性。AMA阴性组和AMA阳性组在临床特征或组织学确定的疾病阶段方面无显著差异。免疫印迹分析显示，所有患者均对四种M2蛋白中的一种或多种具有抗M2自身抗体。15例AMA阴性患者中有9例（60%）仅对一种M2蛋白（70 kDa或47 kDa）有抗体。相比之下，64例AMA高滴度（≥1:320）患者中有34例（53%）对所有四种M2蛋白都有抗体。AMA滴度与抗M2蛋白抗体数量之间存在显著的等级相关性（P<0.01）。这些发现表明，AMA滴度不受M2蛋白免疫原性的影响，而是受引发抗体反应的M2蛋白数量的影响，并且对M2蛋白免疫反应性的降低可能导致PBC血清样本中AMA呈阴性。
