HOST RESPONSE TO HELICOBACTER PYLORI INFECTION

幽门螺杆菌引起的胃炎是当今世界上最常见的慢性感染。它已被国际癌症研究机构(WHO)列为I类人类致癌物。显然，只有很小一部分感染者会患上胃癌。然而，这种肿瘤是世界上第二常见的肿瘤。在美国，某些群体表现出更高的风险，特别是非洲裔美国人、西班牙裔美国人、亚裔美国人以及来自俄罗斯和东欧的移民。这项应用解决了幽门螺杆菌感染的不同结果的问题，在一些受试者中会导致胃癌发生，而在另一些受试者中不会。核心假设是，感染结果的二分法是由免疫力驱动的。拟议的小额赠款申请将使进行可行性研究成为可能，该研究将确定是否有可能对假设进行更明确的检验。我们将重点研究外周血和胃粘膜中淋巴细胞的细胞介导的免疫反应。将进行两个主要比较：a)在哥伦比亚，生活在Nari$o的幽门螺杆菌感染者患胃癌的风险非常高，将与生活在沿海城市卡塔赫纳的感染者进行比较，风险非常低。B)在新奥尔良，被诊断为多发性萎缩性胃炎(MAG)的受试者将与非萎缩性胃炎(弥漫性胃窦炎或DAG)的受试者进行比较，非萎缩性胃炎与胃癌风险增加无关。MAG是癌症的先兆病变。将进行一整套免疫学测试，以探索T淋巴细胞辅助细胞反应(Th1与Th2)的细胞因子特征在对比人群中是否有所不同。如果获得批准，这项申请将使我们能够收集所需的材料，并补充病理学系的其他资源，以便在我们的实验室进行测试。

Gastritis due to Helicobacter Pylori is the most common chronic infection in the world today. It has been classified by IARC (WHO) as a Class I human carcinogen. Obviously only a very small portion of the infected population develops gastric cancer. This neoplasia, however, is the second most frequent in the world. In the United States, certain groups display higher risk, especially African Americans, Hispanics, Asian Americans and immigrants from Russia and Eastern Europe. This application addresses the question of different outcomes of H. Pylori infection, which in some subjects leads to gastric carcinogenesis and in others does not. The central hypothesis is that the dichotomy in outcome of the infection is driven by immunologic forces. The proposed small grant application will make it possible to conduct a feasibility study which will determine if a more definitive test of the hypothesis is possible. We will be focused on the cellular-mediated immune response studied in lymphocytes from the peripheral blood and from the gastric mucosa. Two major comparisons will be done: A) In Colombia H. pylori infected subjects living in Nari$o, at very high gastric cancer risk, will be compared with infected subjects living in the coastal city of Cartagena, at very low risk. b) In New Orleans, subjects diagnosed with multiphocal atrophic gastritis (MAG), a cancer precursor lesion, will be compared with subjects with non-atrophic gastritis (diffuse antral gastritis or DAG), which is not associated with increased gastric cancer risk. A full battery of immunologic tests will be carried out to explore if the cytokines characteristic of the T-lymphocyte helper cells responses (Th1 vs. Th2) are different in the contrasting populations. If approved, this application will make it possible to collect the material needed and complement other resources of the department of Pathology to conduct the tests in our laboratories.