Immune response to Helicobacter pylori VacA as a marker

描述(由申请人提供)： 尽管世界各地的胃癌死亡率正在逐渐下降，但有些国家，特别是东亚地区，这种疾病仍然很普遍。在队列和病例对照研究中，幽门螺杆菌的定植与胃癌密切相关。到目前为止，大多数研究都报告了幽门螺杆菌与胃癌之间的联系，这是通过以幽门螺杆菌的细胞表面制剂池为抗原进行的血清学调查得出的。然而，来自不同地理区域的幽门螺杆菌分离株在基因分型上存在差异。我们建议根据幽门螺杆菌的主要毒力标记(VacA)设计特定的抗原区，并通过评估对这种细菌抗原的免疫反应，确定它是否能更好地预测选定人群中发生胃癌的风险。对于VacA，我们将获得MID区(m1和m2)的特异性多肽抗原，因为初步数据表明，该区域的差异可能是胃癌发展的预测因素。来自夏威夷的日裔美国人的嵌套病例对照研究，血清样本是在他们患上胃癌之前的21年随访中获得的。我们也有未患胃癌的对照个体的血清样本。我们期望发现，与那些没有发生胃癌的患者相比，发生胃癌的患者对一种特定的VacA基因(M1)的免疫反应是主要观察到的。如果我们的假设是正确的，我们希望建立一种简单而经济的血清学测试来评估胃癌发生的风险。

DESCRIPTION (provided by applicant): Although gastric cancer mortality rates are gradually decreasing around the world, there are countries, especially in East Asia in which this disease remains prevalent. Helicobacter pylori colonization has been strongly associated with gastric cancer in cohort and case-control studies. Until now, most studies have reported an association between H. pylori and gastric cancer using serological surveys with pools of cell surface preparations from the bacteria as the antigen. However, H. pylori isolates from different geographic areas vary in genotype. We propose to design specific antigenic regions from the major virulence marker of H. pylori (VacA), and by assessing the immune response to this bacterial antigen, determine whether it is a better predictor for the risk of development of gastric cancer in selected populations. For VacA we will obtain peptide antigens specific for the mid region (m1 and m2) because preliminary data suggests that differences in this region may be a predictor of the development of gastric cancer. From a nested case-control study of Japanese-Americans in Hawaii, serum samples were obtained from individuals before they developed gastric cancer over a 21-year follow-up. We also have serum samples from control individuals who did not develop gastric cancer. We expect to find that the immune response to one particular vacA genotype (m1) is predominantly observed in those patients who developed gastric cancer compared to those in whom gastric cancer did not develop. If our hypothesis is correct, we hope to establish a simple and economical serological test to assess the risk of gastric cancer development.