Antibodies against heat shock protein 60 derived from Helicobacter pylori:: Diagnostic implications in cardiovascular disease

Antibodies against heat shock protein 60 derived from Helicobacter pylori:: Diagnostic implications in cardiovascular disease
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DOI:
10.1016/j.jaut.2007.05.004
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发表时间:
2007-09-01
影响因子:
12.8
通讯作者:
Oguma, Keiji
Oguma, Keiji
中科院分区:
医学1区
文献类型:
--
作者:
Okada, Tomoyuki;Ayada, Kiyoshi;Oguma, Keiji

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针对病原体来源的热休克蛋白60(HSP 60)的免疫应答被认为是防御性事件,其由于分子模拟而误导至人类对应物。因此,动脉粥样硬化可以通过抗HSP 60抗体(Abs)进行血清学预测。在本研究中,我们分析了心血管疾病(CVD; n = 250)患者血清中抗幽门螺杆菌(Hp)衍生的HSP 60(Hp-HSP 60)或其肽段的IgG抗体的临床患病率,并与年龄和性别匹配的非CVD患者(n = 293)进行比较。抗Hp细胞裂解物抗体常出现在与CVD无关的Hp感染患者中。相反,针对特定氨基酸序列Hp-HSP 60(II 3)(Hp-HSP 60中的II 3区,Glu(141)-Leu(160))的Ab主要出现在CVD患者中,以及IgG抗人HSP 60(Hu-HSP 60(w))。抗Hp-HSP 60(113)和抗Hu-HSP 60(w)抗体滴度与hsCRP水平无相关性。提示Hp-HSP 60(Ⅱ 3)抗体与Hu-HSP 60(w)抗体交叉反应是心血管病的独立诊断标志物。此外,20个氨基酸残基(Glu(141)-Leu(160))可能是诱导抗Hu-HSP 60自身抗体的主要CVD相关表位,其位置在Hu-HSP 60的三级结构中被预测。(c)2007爱思唯尔有限公司版权所有。
Immune responses against heat shock protein 60 (HSP60) of pathogen-origin are thought to be defensive events which, due to molecular mimicry, misdirect to a human counterpart. Therefore, atherosclerosis may be serologically predicted by anti-HSP60 antibodies (Abs). In the present study, we analyzed the clinical prevalence of the serum IgG Abs against Helicobacter pylori (Hp)-derived HSP60 (Hp-HSP60) or its peptide fragments in patients with cardiovascular disease (CVD; n = 250), as compared to those in age- and gender-matched non-CVD patients (n = 293). Anti-Hp cell lysate Abs frequently appeared in Hp-infected patients who were not associated with CVD. In contrast, Abs against the particular amino acid sequence Hp-HSP60(II3) (II3 region, Glu(141)-Leu(160), in Hp-HSP60) predominantly appeared in CVD patients, as well as IgG anti-human HSP60 (Hu-HSP60(w)). Furthermore, neither titer of anti-Hp-HSP60(113) nor anti-Hu-HSP60(w) Abs was correlated with the levels of high sensitivity C-reactive protein (hsCRP). This data strongly suggested that IgG anti-Hp-HSP60(II3) Abs cross-reacted with Hu-HSP60(w) were independent diagnostic markers relevant to CVD. Further, the 20 amino acid residues (Glu(141)-Leu(160)) might be predominant CVD-associated epitopes that induce anti-Hu-HSP60 auto-Abs, whose location was predicted in the tertiary structure of Hu-HSP60. (c) 2007 Elsevier Ltd. All rights reserved.