Immune response to Helicobacter pylori VacA as a marker

以幽门螺杆菌 VacA 为标志物的免疫反应

• 批准号: 6695511
• 负责人: GUILLERMO I PEREZ-PEREZ
• 金额: $ 8.44万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-06 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6695511
• 关键词: Helicobacter; Japanese American; antigen antibody reaction; bacterial toxins; biomarker; cancer risk; clinical research; enzyme linked immunosorbent assay; human tissue; infection related neoplasm /cancer; neoplasm /cancer epidemiology; polymerase chain reaction; recombinant proteins; stomach neoplasms; virulence

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.

描述（由申请人提供）： 虽然胃癌死亡率在世界范围内逐渐下降，但仍有一些国家，特别是东亚国家，这种疾病仍然流行。在队列研究和病例对照研究中，幽门螺杆菌定植与胃癌密切相关。到目前为止，大多数研究都报道了H。幽门螺杆菌和胃癌使用血清学调查与池的细胞表面制剂作为抗原的细菌。然而，H.来自不同地理区域的幽门螺杆菌分离株的基因型不同。我们建议从H.幽门螺杆菌（VacA），并通过评估对这种细菌抗原的免疫反应，确定它是否是选定人群中胃癌发生风险的更好预测因子。对于VacA，我们将获得对中间区域（m1和m2）特异的肽抗原，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子。在夏威夷对日裔美国人进行的巢式病例对照研究中，在21年的随访中，从患胃癌前的个体中获得血清样本。我们也有来自未患胃癌的对照个体的血清样本。我们期望发现，与未发生胃癌的患者相比，发生胃癌的患者主要观察到对一种特定vacA基因型（m1）的免疫应答。如果我们的假设是正确的，我们希望建立一个简单和经济的血清学试验，以评估胃癌的发展风险。