Targeting B cell-mediated Type II Autoimmunity in Gastric Carcinogenesis
Technical Report,01 Aug 2017,31 Jul 2018
Regents of the University of Michigan Ann Arbor United States
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The purpose of this project is to evaluate the contribution of gastric B cells to the development of gastric pre-neoplastic lesions in response to Helicobacter infection. The conclusion of the project will be a pre-clinical evaluation of utilizing rituximab anti-CD20 to ameliorate gastric metaplastic lesions in this setting. The relevance to the military is due to deployment in areas with prevalent Helicobacter pylori H. pylori contamination, even in the drinking water in certain areas, which increase the risk to military personnel and veterans. Long-term H. pylori infection induces gastric pre-neoplastic lesions, which increase the risk of gastric cancer. If positive, the outcome will propose the use of rituximab to reduce the risk of carcinogenic development in military personnel exhibiting gastric metaplastic lesions due to ongoing or previous H. pylori infection. The aims of years 1 and 2 are to 1 describe the specific nature of B cells in the Helicobacter-infected stomach subtypes, functions and interaction with T cells, and 2 the downstream activities that contribute to disease. Year 3 will test the preclinical assay with rituximab. Year 1 has successfully i set up the necessary mouse models and 6-month infections for year 2 analyses, and ii generated transcriptional heat maps of gastric B cell subsets. These outcomes and progress will be described in the report in more detail.
- Medicine and Medical Research