Function Of Factor H-related Protein-5, A Novel Human Plasma Complement Protein Found In Glomerular Immune Deposits
Funder
National Health and Medical Research Council
Funding Amount
$186,430.00
Summary
The Investigators have recently discovered a new protein which is present in human blood and is also seen in the diseased kidneys of patients with nephritis. The new protein is present in all types of nephritis that are caused by antibodies together with another part of the immune system, called the complement system, which is know to have an important role in causing tissue damage in immune diseases. The new protein is a part of the complement system but its exact function is not yet known. The ....The Investigators have recently discovered a new protein which is present in human blood and is also seen in the diseased kidneys of patients with nephritis. The new protein is present in all types of nephritis that are caused by antibodies together with another part of the immune system, called the complement system, which is know to have an important role in causing tissue damage in immune diseases. The new protein is a part of the complement system but its exact function is not yet known. The protein is likely to be important in immune diseases because it is so commonly found in diseased kidneys and other organs with complement-associated disease. In this project we will conduct a series of experiments which will determine how the new protein works in the complement system and also how important the protein is in causing kidney damage in nephritis. Nephritis is the commonest cause of kidney failure in Australia and research directed towards the mechanism of kidney damage has the potential to produce new types of therapy. The complement system also has a major role in other inflammatory diseases and in body defense systems (such as protection against microbial attack). The complement system must be able to distinguish between foreign particles and the body's own tissue and this new protein may have a role in the appropriate regulation of complement to attack the right things in the body. Elucidation of the function of this protein may well assist, therefore, in developing therapies for a variety of inflammatory diseases and infectious diseases, in addition to nephritis.Read moreRead less
Glomerulonephritis (Bright's Disease) is the commonest cause of destruction of kidney function that leads to patients requiring artificial kidney treatment (dialysis) and renal transplantation. The glomeruli or filters of the kidney are attacked by inflammation and destroyed. The attack is usually auto-immune, that is the bodys' immune system loses tolerance to kidney tissue and mounts a destructive attack on the glomeruli. In many patients, this attack is mild and resolves with current treatmen ....Glomerulonephritis (Bright's Disease) is the commonest cause of destruction of kidney function that leads to patients requiring artificial kidney treatment (dialysis) and renal transplantation. The glomeruli or filters of the kidney are attacked by inflammation and destroyed. The attack is usually auto-immune, that is the bodys' immune system loses tolerance to kidney tissue and mounts a destructive attack on the glomeruli. In many patients, this attack is mild and resolves with current treatments to dampen the immune response. In others, current treatment is inadequate to dampen the attack and the kidney is destroyed. This research uses experimental models of nephritis to examine how the immune system injures the glomeruli. In particular, how T cells attack and mediate injury. This is a novel concept, as hither to it has been thought antibodies and other factors in the blood (complement) mediate injury. Our group was one of the first to identify T cells mediate injury in forms of glomerulonephritis, previously thought to be solely mediated by antibody and complement. This project will further define which molecules produced by the T cell effect injury of glomeruli. With the potential aim of turning off the T cell attack mechanisms in a more specific way than is achieved by non specific immunosuppressive drugs such as corticosteroids, cytotoxic (anti-cancer) drugs or cyclosporine (an anti-rejection drug). A major part of this project will be to examine the role of cytokines, hormone like molecules that are produced by white cells and mediate injury or regulate other white cells, in effecting injury and in turning off the immune injury.Read moreRead less