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）列为一类人类致癌物。显然，只有一小部分感染人群会发展成胃癌。然而，这种肿瘤是世界上第二常见的肿瘤。在美国，某些群体的风险更高，尤其是非洲裔美国人、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。该应用解决了幽门螺杆菌感染的不同结果的问题，在一些受试者中导致胃癌，而在另一些受试者中则不会。中心假设是感染结果的二分法是由免疫力量驱动的。拟议的小额赠款申请将能够进行可行性研究，以确定是否有可能对该假设进行更明确的检验。我们将重点研究外周血淋巴细胞和胃粘膜细胞介导的免疫反应。将进行两项主要比较：A)在哥伦比亚，将居住在Nari$o的幽门螺杆菌感染受试者与居住在沿海城市Cartagena的感染受试者进行比较，前者胃癌风险非常高，后者风险非常低。b)在新奥尔良，诊断为多腔萎缩性胃炎（MAG）的受试者将与非萎缩性胃炎（弥漫性胃炎或DAG）的受试者进行比较，MAG是一种癌症前驱病变，与胃癌风险增加无关。将进行全套免疫学测试，以探索t淋巴细胞辅助细胞反应（Th1 vs. Th2）的细胞因子特征在对比人群中是否不同。如果获得批准，该申请将有可能收集所需的材料，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.