Uehara Soichiro, Gotoh Katsuhiro, Handa Hiroshi, Tomita Hiroshi, Senshuu Mitiko
Department of Internal Medicine and Gastroenterology, Ohtakionsen Hospital, Hokkaido, Japan.
J Gastroenterol Hepatol. 2005 Oct;20(10):1545-52. doi: 10.1111/j.1440-1746.2005.03899.x.
Our aim was to evaluate the heterogeneity of des-gamma-carboxyprothrombin (DCP) in the plasma of patients with hepatocellular carcinoma (HCC), benign liver diseases, and normal controls and compare the DCP values by enzyme-linked immunosorbent assay (ELISA) for two types monoclonal antibodies (MU-3 and 19B7).
We purified DCP from the plasma of 17 patients with HCC, three patients with metastatic liver tumors (MTLT), 12 with acute hepatitis (AH), five with chronic hepatitis (CH), nine with liver cirrhosis (LC), and 10 normal controls (NC). The DCP was analyzed by using immunoaffinity chromatography, reversed-phase high-performance liquid chromatography and measured by using an ELISA.
In HCC, the synthesis of the 1-, 3-, and 4-Gla (gamma-carboxyglutamic acid) DCP variants markedly increased, and those levels accounted for more than 50% of the DCP. The synthesis of the 3-, and 4-Gla DCP gradually increased in order of AH, CH, and LC patients. The MU-3 antibody reacted with the 1-, 3- and 4-Gla DCP variants, whereas the 19B7 antibody reacted with the 6-, 7- and 8-Gla variants. The DCP was measured by ELISA, markedly increased in order of NC, AH, CH, LC, and HCC cases. The correlation of the ratios (1 + 3 + 4)-Gla/(6 + 7 + 8)-Gla DCP and MU-3/19B7 was positive and statistically significant (r = 0.786, n = 56).
According to the severity of liver damages, the synthesis of the 1-, 3- and 4-Gla DCP variants that lost the Ca binding from the outside of the Gla-domain of the prothrombin molecule increases and the MU-3/19B7 ratio is believed to reflect this.
我们的目的是评估肝细胞癌（HCC）患者、良性肝病患者及正常对照者血浆中去γ-羧基凝血酶原（DCP）的异质性，并通过酶联免疫吸附测定（ELISA）比较两种单克隆抗体（MU-3和19B7）检测的DCP值。
我们从17例HCC患者、3例转移性肝肿瘤（MTLT）患者、12例急性肝炎（AH）患者、5例慢性肝炎（CH）患者、9例肝硬化（LC）患者及10例正常对照者（NC）的血浆中纯化DCP。采用免疫亲和色谱法、反相高效液相色谱法对DCP进行分析，并通过ELISA进行检测。
在HCC患者中，1-、3-和4-γ-羧基谷氨酸（Gla）DCP变体的合成显著增加，且这些水平占DCP的50%以上。3-和4-Gla DCP的合成在AH、CH和LC患者中按顺序逐渐增加。MU-3抗体与1-、3-和4-Gla DCP变体反应，而19B7抗体与6-、7-和8-Gla变体反应。通过ELISA检测DCP，其在NC、AH、CH、LC和HCC病例中按顺序显著增加。（1 + 3 + 4）-Gla/（6 + 7 + 8）-Gla DCP比值与MU-3/19B7的相关性为正且具有统计学意义（r = 0.786，n = 56）。
根据肝损伤的严重程度，凝血酶原分子Gla结构域外失去Ca结合的1-、3-和4-Gla DCP变体的合成增加，且MU-3/19B7比值被认为可反映这一情况。
