Detection of autoantibody to aldolase B in sera from patients with troglitazone-induced liver dysfunction
Detection of autoantibody to aldolase B in sera from patients with troglitazone-induced liver dysfunction
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DOI：
10.1016/j.tox.2005.07.012
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发表时间：
2005-12-01
期刊：
影响因子：
4.5
通讯作者：
Yokoi, T
中科院分区：
文献类型：
--
作者：
Maniratanachote, R;Shibata, A;Yokoi, T
曲格列酮是一种具有胰岛素增敏活性的噻唑烷二酮降糖药，由于其与特异质肝毒性相关，于2000年退出市场。为了解决与曲格列酮相关的可疑自身抗体产生，我们研究了曲格列酮诱导的肝功能障碍的II型糖尿病患者血清中的自身抗体。2例女性患者（47岁和70岁）分别在23.5周和16周后因血清ALT升高而停用曲格列酮（400 mg/天）。使用二维电泳和氨基酸序列分析，醛缩酶B被确定为一种自身抗原，与两名患者血清中的抗体反应。停止曲格列酮给药后，抗醛缩酶B的滴度在数周内仍保持较高水平。用ELISA法测定的慢性肝炎（n = 40）和肝硬化（n = 40）患者血清对醛缩酶B的自身抗体的平均反应性显著高于健康人（n = 80）（分别为P < 0.05和P < 0.001）。这些结果表明，肝损伤可能会导致醛缩酶B自身抗体的出现，然后可能加重肝炎。此外，抗醛缩酶B滴度可指示肝功能障碍的严重程度。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Troglitazone is a thiazolidinedione antidiabetic agent with insulin-sensitizing activities that was withdrawn from the market in 2000 due to its association with idiosyncratic hepatotoxicity. To address the suspected autoantibody production associated with troglitazone, we investigated autoantibodies in sera from patients with type II diabetes mellitus with troglitazone-induced liver dysfunction. Two female patients (47- and 70-year-old) ceased taking troglitazone (400mg/day) after 23.5 and 16 weeks, respectively, due to increased serum ALT. Using two-dimensional electrophoresis and amino acid sequence analyses, aldolase B was identified as an autoantigen that reacted with antibodies in sera from both patients. The titer of anti-aldolase B remained high for several weeks after stopping troglitazone administration. The mean reactivity of autoantibodies to aldollase B determined by ELISA with sera of patients with chronic hepatitis (n = 40) and liver cirrhosis (n = 40) was significantly higher (P < 0.05 and p < 0.001, respectively) than with sera of healthy subjects (n = 80). These findings suggest that liver injury may cause the appearance of autoantibodies to aldolase B which may then aggravate the hepatitis. In addition, the anti-aldolase B titer might indicate the severity of liver dysfunction. (c) 2005 Elsevier Ireland Ltd. All rights reserved.