A Functional Genomic Approach To The Genetics Of Autoimmune (type A) Gastritis
Funder
National Health and Medical Research Council
Funding Amount
$467,640.00
Summary
The thymus produces white blood cells which defend the body from infections and cancer. Unfortunately, these white blood cells can also cause disease if they target the body's own tissues. These disesaes are called autoimmune diseases, and an example of such a disease is autoimmune (type A) gastritis, in which the white cells target the acid-producing cells of the stomach. The resulting damage can lead to the development of pernicious anaemia (vitamin B12 deficiency) and cancer of the stomach. T ....The thymus produces white blood cells which defend the body from infections and cancer. Unfortunately, these white blood cells can also cause disease if they target the body's own tissues. These disesaes are called autoimmune diseases, and an example of such a disease is autoimmune (type A) gastritis, in which the white cells target the acid-producing cells of the stomach. The resulting damage can lead to the development of pernicious anaemia (vitamin B12 deficiency) and cancer of the stomach. This project studies a mouse model of autoimmune gastritis with the aim of identifying the genes that encode susceptibility to the disease in this model. Ultimately, this information should help us to devise therapies that can be applied to the clinical situation. We have previously identified the locations of the genes which are responsible for causing gastritis in these mice. Two of them are very close together on one chromosome and appear to be very important because they have the strongest effects. Furthermore, there is some evidence that these genes may also be involved in determining susceptibility to diabetes and lupus. This project aims to further characterise these genes by locating them more exactly and by examining their effect on mice not normally prone to gastritis.Read moreRead less
Genetic Pathology Of Roquin In Human Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$495,466.00
Summary
Lupus is a life-threatening disease in which immune responses normally targeted at germs are directed at tissue in the body. We have discovered a mouse model of lupus and elucidated an important pathway that determines whether immunity is directed at the body or at germs. Building on recent progress in understanding the genetic variation between individuals, we will use the information obtained from the mouse model to investigate the genes that regulate this pathway in people with lupus.
Initiation And Diversification Of Systemic Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$200,749.00
Summary
One of the striking findings in autoimmune diseases such as systemic lupus erythematosus and Sjogren's syndrome is the presence in the blood of autoantibodies reacting with certain proteins or autoantigens. The best known autoantigens are termed La and Ro and are important diagnostic markers in these two common conditions. It appears that the immune response starts against Ro and then spreads to La over time, a process known as epitope spreading. There is emerging evidence in Sjogren's syndrome ....One of the striking findings in autoimmune diseases such as systemic lupus erythematosus and Sjogren's syndrome is the presence in the blood of autoantibodies reacting with certain proteins or autoantigens. The best known autoantigens are termed La and Ro and are important diagnostic markers in these two common conditions. It appears that the immune response starts against Ro and then spreads to La over time, a process known as epitope spreading. There is emerging evidence in Sjogren's syndrome that the severity of this condition is related to the degree of epitope spreading to Ro and La, which in turn is controlled by the genetic background of the individual. We therefore wish to study the initiation of the autoimmune response to Ro and the factors which influence spreading or diversification to La, using a mouse model of La-Ro autoimmunity which we have developed. In addition, we shall investigate the potential role of a recently identified gene in a large group of patients with Sjogren's syndrome. We believe this gene may control the epitope spreading and expression of disease. The role of other molecules called chaperones (which bind to Ro) and complement (involved in clearing dead cells which may trigger autoimmunity) will also be studied. The ultimate goal of the work is to develop ways of blocking the epitope spreading which should ameliorate the disase and patients' symtpoms.Read moreRead less