Maruyama T, McLachlan A, Iino S, Koike K, Kurokawa K, Milich D R
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037.
J Clin Invest. 1993 Jun;91(6):2586-95. doi: 10.1172/JCI116497.
The serology of chronic hepatitis B infection has been established through the use of commercial immunoassays to measure the structural antigens of the hepatitis B virus and their respective antibodies in serum. However, the commercial assays have not been designed to detect serum antibodies in the presence of an excess of circulating antigens. A series of serum samples from 200 HBeAg-positive, chronically infected hepatitis B patients with varying degrees of liver disease were analyzed using novel immunoassays designed to detect antibodies in the presence of circulating viral antigens. All patients, regardless of their liver disease, were seronegative for antibodies specific for the envelope antigens or the secreted nucleoprotein antigen (HBeAg) when the commercial assays were used. In contrast, virtually all chronically infected patients with liver disease and approximately 50% of patients without liver disease demonstrated anti-HBe and anti-envelope antibodies when sera were tested in the more sensitive immunoassays. Furthermore, asymptomatic patients could be serologically distinguished from symptomatic patients based on antibody fine specificity, titer, and IgG subclass. This study revealed that the majority of chronically infected hepatitis B patients produce a variety of antibodies for many years, and are not immunologically unresponsive, as suggested by the current assays.
慢性乙型肝炎感染的血清学检测是通过使用商业免疫测定法来测量血清中乙型肝炎病毒的结构抗原及其相应抗体而建立的。然而，商业检测方法并非设计用于在存在过量循环抗原的情况下检测血清抗体。使用旨在在存在循环病毒抗原的情况下检测抗体的新型免疫测定法，对200例HBeAg阳性、慢性感染乙型肝炎且患有不同程度肝病的患者的一系列血清样本进行了分析。当使用商业检测方法时，所有患者，无论其肝病情况如何，针对包膜抗原或分泌型核蛋白抗原（HBeAg）的特异性抗体均为血清阴性。相比之下，当在更敏感的免疫测定法中检测血清时，几乎所有患有肝病的慢性感染患者以及约50%无肝病的患者都显示出抗-HBe和抗包膜抗体。此外，无症状患者可根据抗体的精细特异性、滴度和IgG亚类在血清学上与有症状患者区分开来。这项研究表明，大多数慢性感染乙型肝炎的患者多年来会产生多种抗体，并非如目前检测方法所暗示的那样免疫无反应。
