The etiology of autoimmune diabetes is not known. However, the disease is accompanied by varying amounts of immune activation and inflammation. Although genetics clearly plays a role in determining who gets the disease, we do not know the instigating events. There has been a lot of investigation into the potential role of virus infections in triggering disease. However, there are no direct associations known between virus and disease in humans.

Recently, there has been increased interest in issues such as intestinal permeability and the microbiome in diabetes patients. One theory is that the leaky gut in T1D patients allows the penetration of bacteria and/or their products into the body, causing immune stimulation. When such products arrive into the pancreas after draining from the ducts, they cause changes in gene expression and inflammation. One set of factors that would get induced is bactericidal proteins, whose expression or subcellular localization is affected by exposure to bacterial products.

We have studied the expression of bactericidal proteins in circulation in new onset T1D patients. These studies indicated that there were coordinately high levels of expression in circulation in T1D patients less that five years after disease onset. These results suggest the upregulation of anti-bacterial responses in T1D patients. In this project, we will determine whether bactericidal factors are upregulated in the pancreas in T1D patients.

This project is important because it will tell us whether the disease may be mediated by the release of bacteria or their products into the pancreas, which would cause immune activation and inflammation. Several different bactericidal response elements will be investigated, each reflecting exposure to different bactericidal products including DNA, cell membrane constituents, and pigment molecules, an each providing an indication of the type of exposure the pancreas has encountered.