There has been no significant breakthrough in the treatment of Systemic Lupus Erythematosus (SLE) for over 50 years. Treatment continues to rely on non-specific immunosuppressant drugs and glucocorticoids (GC, or ‘steroids’), and the impact on patients includes high mortality and poor quality of life. In this proposal, I will validate novel endpoints which will break the impasse in SLE drug development and develop tools for minimising GC use in SLE.
Links Between Inflammatory Activity, Autoantibodies, And Cardiovascular Disease In Patients With SLE.
Funder
National Health and Medical Research Council
Funding Amount
$32,003.00
Summary
People with lupus are at increased risk of heart attack and stroke. For women aged 30-44 the risk is as much as fifty times higher than in women without lupus. Only some of this risk is due to well known factors like high blood pressure and cholesterol. We are looking at other possible causes of heart attack and stroke in people with lupus - with blood tests and heart scans. We hope this will identify who is at risk and what can be done to prevent them from suffering a heart attack or stroke.
Targeting Autophagy As A Means Of Control Of Cytokine Production In SLE
Funder
National Health and Medical Research Council
Funding Amount
$616,518.00
Summary
Systemic lupus erythematosus (SLE, or lupus) is a common immune disease that causes organ damage and loss of life, chiefly affecting young women. There is no cure for SLE. We have discovered that a natural process called 'autophagy' could be a way to limit inflammation during SLE. In this project we will discover whether this could lead to a new way to treat this disease.
Novel Mechanisms And Targets In Neonatal Lupus: Clues To Systemic Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$428,250.00
Summary
Autoimmune diseases represent the third greatest clinical burden to the community after heart disease and cancer. Management of the diseases remains primitive because of our poor understanding of the disease mechanisms. Autoantibodies are one of the key markers of diseases such as lupus and Sj gren's syndrome, but their role in producing tissue damage is largely unresolved. However in the neonatal lupus syndrome, autoantibodies from the mothers cross the placenta and appear to cause inflammation ....Autoimmune diseases represent the third greatest clinical burden to the community after heart disease and cancer. Management of the diseases remains primitive because of our poor understanding of the disease mechanisms. Autoantibodies are one of the key markers of diseases such as lupus and Sj gren's syndrome, but their role in producing tissue damage is largely unresolved. However in the neonatal lupus syndrome, autoantibodies from the mothers cross the placenta and appear to cause inflammation of particular target organs such as the heart and skin in the babies. Neonatal lupus offers a unique opportunity to investigate the pathological role of autoantibodies and other factors (e.g. infection) in autoimmune diseases, and is likely to offer vital clues to lupus in adults. For example, the skin disease in babies with lupus mimics the cutaneous lesions in adult lupus patients. Recent work from our group using an animal model has shown that certain autoantibodies cross the placenta and bind to cells undergoing physiological death in the fetus, in the same organ distribution as human neonatal lupus. Using sophisticated imaging techniqes we can now trace the fate of maternal autoantibodies in the babies for the first time and understand how the target proteins in heart and skin become exposed to the damaging effects of these autoantibodies. We also believe that certain types of autoantibodies can directly alter contraction and electrical activity in the heart in babies with neonatal lupus, leading to heart block which can be fatal. We have already discovered similar functional autoantibodies in adult patients with Sj gren's syndome whose babies can also also develop neonatal lupus, and plan to characterise them using unique physiological assays in intact hearts. We will characterise the redistribution of antigenic proteins in cells in fetuses and the interaction of maternal autoantibodies with these proteins to cause tissue damage and functional heart block.Read moreRead less
The Role Of Myeloperoxidase In Adaptive Immunity And The Development Of Experimental Glomerulonephritis And Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
This proposal will explore the role of key defensive enzyme in white blood cells, myeloperoxidase. It participates in immune defence as well as autoimmune diseases including nephritis and arthritis. This study will define the mechanisms of its protective and injurious capacities in these diseases.
This project introduces a new biomarker in systemic lupus erythematosus termed an apotope. The aims are to study the diagnostic potential of an apotope of Ro60, a key target in lupus, together with its ability to initiate the disease and cause organ damage. The interaction of the Ro60 apotope with a novel protective factor called beta2-glycoprotein I will also be studied. These discoveries are likely to lead to new diagnostic tests and preventions for lupus and neonatal lupus.
Rogue B Cell Clones In Patients With Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$916,670.00
Summary
Our immune system protects us from disease by producing antibodies. However, 5% of Australians suffer from an autoimmune disease where they produce “auto” antibodies, which attack their own organs. This research will study the cells (termed B cells) responsible for making autoantibodies to determine how they differ from B cells that defend against disease. The goal is to develop therapies that eliminate autoantibody producing B cells from patients while preserving the immune system.
Exploring The Contribution Of Interferon-lambda To Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$833,235.00
Summary
We have found that a novel protein, normally made in response to viral infections, is found in the blood of Lupus patients. This project will determine the cells that make this protein, what in Lupus blood makes these cells produce it and whether it plays a role in the severity of Lupus disease.
Optimising Osteoporosis Management In Young Adults
Funder
National Health and Medical Research Council
Funding Amount
$132,743.00
Summary
Fragility fractures contribute to reduced quality of life in younger adults with chronic disease. However, tools for predicting these fractures and evidence for the best treatment to prevent them is lacking in this group. We aim to address these gaps in evidence through assessment of bone health in younger adults with two chronic diseases related to increased inflammation of either the bowel or joints, as they are the two leading conditions resulting in fragility fractures in younger adults.
Role Of Adhesion Molecules In Autoimmune Vasculitis
Funder
National Health and Medical Research Council
Funding Amount
$377,036.00
Summary
Lupus is a disease which causes inflammation and pain throughout the body. The inflammation is caused by white blood cells attacking the lining of blood vessels in tissues. The aim of this project is to understand the reasons why these white blood cells attack the blood vessel lining. This process is impossible to study in humans. However, there is a strain of mouse which is affected by a disease which is very similar to human lupus. This disease occurs spontaneously in these mice. Using a micro ....Lupus is a disease which causes inflammation and pain throughout the body. The inflammation is caused by white blood cells attacking the lining of blood vessels in tissues. The aim of this project is to understand the reasons why these white blood cells attack the blood vessel lining. This process is impossible to study in humans. However, there is a strain of mouse which is affected by a disease which is very similar to human lupus. This disease occurs spontaneously in these mice. Using a microscope, it is possible to study the tiny blood vessels which are affected by this disease in these mice . Under the microscope, it is possible to see the white blood cells as they undergo the process of attacking the blood vessel lining. Visualizing this attack then allows us to study it and determine which molecules are important in causing this damaging inflammatory response. Specifically I will examine diseased blood vessels in the skin and brain of these mice, two of the tissues most dramatically affected by this disease. This information should help us gain an increased understanding of lupus as it affects humans.Read moreRead less