Initiation and diversification of systemic autoimmunity

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/102139

Funding Status
Closed

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Funded Activity 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 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.

Funded Activity Details

Start Date: 01-01-2000

End Date: 01-01-2002

Funding Scheme: NHMRC Project Grants

Funding Amount: $200,749.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Emergency medicine

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Clinical and serological assessment of rheumatology patients | La and Ro nuclear autoantigen interactions with chaperones | La/Ro epitope spreading in Sjogren's syndrome | Sjogren's syndrome | autoimmune diseases | genetic control of autoimmunity by MHC genes | murine model of autoimmunity | systemic lupus erythematosus | systemic rheumatic diseases

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