A new model for the pathogenesis of rheumatic fever: superantigen priming of the immune response to group A streptococci

Funded Activity Summary

Acute rheumatic fever (ARF) is now rare in developed countries. However, it remains a major problem in Aboriginal Australians in the NT where the rate of ARF is the highest in the world. This leads to high rates of rheumatic heart disease (up to 3% of individuals in some communities) and a premature mortality of over four times that for developing countries. Immunisation and improved living conditions offer a long-term solution but these remain a distant prospect. In the short and medium term, control of this ARF will partly depend on new and better treatment and prevention strategies. To achieve these goals a deeper understanding of the immune mechanisms underlying this disease is urgently needed. It is known that ARF is caused by an abnormal immune response following streptococcal infection. This leads to the production of cells called T cells that attack the body s own tissues rather than the bacteria itself. This autoimmune disease is responsible for the heart damage that underlies ARF. It is believed that this proces only occurs when susceptible individuals are infected with specific rheumatogenic strains of streptococci. However there are a number of deficiencies in this model and it is proposed that there is an additional factor responsible for the abnormal immune response in ARF. This project will explore the possibility that bacterial toxins called superantigens are the critical missing factor , by studying the immune response in ARF. Superantigens are produced by certain streptococci and staphylococci, and are potent in minute quantities causing widespread activation of the immune system. They have been found to play an important role in a number of autoimmune diseases and the type of immune response found in ARF fits well with that expected if superantigens were involved. If superantigens play an important role in causing the abnormal immune response in ARF then a number of new avenues would open for the treatment and prevention of this disease.

Funded Activity Details

Start Date: 01-01-2002

End Date: 01-01-2004

Funding Scheme: NHMRC Project Grants

Funding Amount: $248,820.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Infectious Diseases

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Aboriginal Health | Aboriginal health | Bacterial exotoxins | Group A streptococcal disease | Rheumatic fever | Superantigens

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