Centre for Inflammatory Diseases

Kidney disease immunology

Groups leaders: Professor Stephen Holdsworth & Associate Professor Richard Kitching

Glomerulonephritis (GN) is a common cause of end stage renal failure. In our bid to identify potential therapeutic targets, the overall aim of our group’s research is to further our understanding of:

• Key events in the generation of nephritogenic immune responses
• Autoimmunity as it pertains to the kidney
• Effector responses in the kidney

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 leucocytic influx) 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)

• The mechanisms by which effectors, particularly leucocytes, are recruited to glomeruli, including the interactions between the kidney and the immune system in these processes

Newer research areas being explored include:

• The role of renal dendritic cells in immune renal injury
• The nature of the loss of tolerance to alpha 3(IV)NC1 (the antigen responsible for Goodpasture’s disease) and to myeloperoxidase