|The Monash Health Vasculitis Clinic|
World-class research and treatment of kidney disease
Autoimmune Kidney Disease and Vasculitis Research Group
We are working on the genetic influences that predispose people to developing vasculitis and lupus with the NHMRC funded Centre for Personalised Immunology. It is the aim of this centre to use personalised and therefore more specific treatments for people with autoimmune disease.
Glomerulonephritis (GN) is not a single disease, but results from damage to the glomerular microcirculation from injurious immune responses to endogenous and foreign antigens in glomeruli. Crescentic GN, a major focus of our research, is named because of the characteristic accumulation of cells (resulting from severe leukocyte mediated glomerular inflammation) in the shape of a crescent. This characterises the most severe forms of GN, which also have the worst health outcomes. Several different diseases cause crescentic GN, the most common being small vessel vasculitis resulting from autoimmunity to neutrophil granules including myeloperoxidase.
Collaborating with our research partners, we are testing hypotheses relating to the following areas of how immune responses induce renal injury:
- The signals that result in the resultant strength and direction of the immune response, especially T-cell polarisation (including Th1/Th2 and Th17).
- The mechanisms by which effectors, particularly leucocytes, are recruited to glomeruli, including the interactions between the kidney and the immune system in these processes.
- Studies in patients determining the critical peptides inducing autoimmunity, the nature of these injurious immune responses and the abnormality of tolerance that underlie them.
- Studies defining how antibodies induce glomerular leukocyte influx.
- Critical molecular pathways and cells inducing injury that may be therapeutic targets.
Newer research areas being explored include:
- The role of renal dendritic cells in immune renal injury.
- The nature of the loss of tolerance to a3(IV)NC1 (the antigen responsible for Goodpasture's disease and to myeloperoxidase.
This systemic disease often targets the kidney causing severe glomerulonephritis, but current treatments are toxic and non-specific. Recent data convincingly confirms this is an autoimmune disease. Clinical and experimental studies of the group are establishing new ways by which the kidneys are attacked, as well as defining parts of the disease-initiating autoantigen that can be targeted to modify disease. This knowledge will be focussed on designing novel vaccination strategies to treat disease in humans.