Autoimmune Kidney Disease and Vasculitis Research Group

Vasculitis is inflammation of the blood vessels. While in essence it sounds relatively harmless vasculitis can lead to serious organ damage, especially in the kidneys (the condition effectively turns the body's immune system on itself).

White blood cells are central to the development of severe forms of human glomerular inflammation. They are also increasingly recognised as important in acute kidney (renal) injury, a common complication of hospital stays that increases the chance of a poor clinical outcome. Studies of human kidney biopsies and immune cells, as well as relevant animal models, help define the critical molecular steps in the induction of these types of injury and provide novel therapeutic targets for new and less toxic therapies.

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis is a type of autoimmune disease which affects small blood vessels. Normally, antibodies are produced by white blood cells to help fight infection, but in ANCA associated vasculitis, abnormal autoantibodies are formed which attack one's own cells or tissues; specifically a white blood cell called a neutrophil.

Vasculitis research at Monash

Autoimmune Kidney Disease and Vasculitis Research Group is working to better understand the mechanism of disease in ANCA vasculitis in order to define specific, less toxic therapies for this disease. Finding targeted treatments that produce fewer side-effects and greater quaility of life is a key aspect of our work.

Our researchers are clinician-scientists - a typical day at work might see them in the lab conducting research, teaching medical students face-to-face or online, and seeing patients in our clinics.

The Monash Health Vasculitis Clinic

The new Monash Health Vasculitis Clinic, led by nephrologist and physician-scientist Professor Richard Kitching, from the Monash Health Department of Nephrology, and the Centre for Inflammatory Diseases (CID) in the School of Clinical Sciences at Monash Health, is a collaboration between renal (kidney) medicine and rheumatology.

Prof Richard Kitching Youtube video (1:44min): Monash discovery points towards more targeted treatments for vasculitis

Our research partner

The RELENT project

Vasculitis Australia

Our aim

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.

More about vasculitis View

Vasculitis may not be as well-known as its autoimmune disease cousins lupus and multiple sclerosis (MS), however improving outcomes for patients with this debilitating, often fatal and little-known inflammatory disease is a key research focus for clinician-scientists in the School of Clinical Sciences at Monash Health.

What are the symptoms?

ANCA vasculitis varies in severity and may result in inflammation in a number of organ systems. Fever, joint aches, skin rash, and fatigue are common symptoms. There may also be involvement of the eyes, sinuses, gastrointestinal tract and nervous system. Bleeding into the lungs, called pulmonary haemorrhage, and kidney involvement, called ANCA associated glomerulonephritis, are the most severe manifestations and may be life threatening.

Who does it affect?

Although lacking the profile of other autoimmune diseases, vasculitis in Australia has a similar incidence to MS; 1/50,000 people, and most common in people aged 65-74 years. Genetic and environmental factors can both play a role in the development of this disease. Without treatment, 85 per cent of patients with vasculitis currently die within five years. Even with treatment, up to 30 per cent of patients die and half of those die from the treatment itself.

Treatment of vasculitis

Treatment of vasculitis depends on the severity and the organ system involved. Left untreated, severe vasculitis results in very poor outcomes. Current treatment options for severe vasculitis are medications like steroids, cyclophosphamide and rituximab, which supress the immune system and therefore aim to improve the autoantibody related inflammation. However, these medications are non-specific and associated with serious side effects, most prominently an increased risk of infection and an increased risk of cancer with cyclophosphamide.

Recommended vasculitis resources

For more information we recommend these resources:

Meet the team View

Research interests View

RELapses prevENTion in chronic autoimmune disease: common mechanisms and co-morbidities (RELENT) is a multidisciplinary group of scientists and clinical investigators whose goal is to develop individualized treatment for chronic autoimmune diseases, such as rheumatoid arthritis and vasculitis. These diseases cause considerable mortality and morbidity, both from uncontrolled disease and treatment associated co-morbidities, like infection and malignancy. This requires the need to stratify patients by their outcome and to tailor immunosuppression based on much deeper knowledge of the mechanisms that control initiation and persistence of the pathogenic immune responses. Find out more.
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.

Clinical Sciences at Monash Health

Medicine, Nursing and Health Sciences