Preventing Infections In Patients With Blood Cancer Through Evidence-based Use Of Immunoglobulin Or Alternatives: The RATIONALISE Trial
Funder
National Health and Medical Research Council
Funding Amount
$2,490,421.00
Summary
Patients with blood cancers, with immune deficiency from low antibody levels and other disease or treatment factors, are at risk of life-threatening infection. Immunoglobulins (Ig) made from plasma can supplement antibody levels. Government criteria recommend stopping Ig therapy in stable patients, but with no evidence for when or how to do so. RATIONALISE will provide this evidence, to improve patient outcomes, reduce risks and costs, and make better use of blood products for the community.
The Control Of Autoimmunity Originating From Somatically Hypermutated B Cells
Funder
National Health and Medical Research Council
Funding Amount
$530,337.00
Summary
Our immune systems are capable of producing long-lived antibodies that can last a lifetime. Sometimes, this powerful process can however become abnormal and result in autoimmune diseases such as lupus. We have recently developed the first experimental mouse model that allows researchers to study this process in great detail. This funding will extend our initial observations by identifying the exact mechanisms by which important regulators of autoimmune disease act.
Lymphocyte Differentiation And Genetics Of Primary Immunodeficiency
Funder
National Health and Medical Research Council
Funding Amount
$143,676.00
Summary
Primary immunodeficiency diseases affect a large number of individuals. Due to abnormal immune responses, these people are at risk of frequent, severe infections, as well as complications of autoimmune disease and cancer. Treatment often involves regular immunoglobulin (antibody) replacement. Through a better understanding of the mechanisms underlying these immunodeficiency diseases, we hope to be able to determine genetic causes, and more cost-effective and targeted treatment options.
Nodal Function In Peripheral Neuroinflammatory Disorders: Target Antigens, Functional Significance And Treatment Response
Funder
National Health and Medical Research Council
Funding Amount
$605,172.00
Summary
Inflammatory neuropathies are autoimmune disorders which produce severe disability and represent a costly burden to the healthcare system, but the causes remain unknown. Recent evidence from our team suggests that antibodies against parts of the peripheral nerve at the node of Ranvier are involved. The project aims to identify these specific targets and monitor treatment responsiveness, stabilise nerve function and prevent persistent disability.
We have discovered how a rare type of human antibody called IgG4 exerts a major regulatory influence on the body's immune system. We have discovered how IgG4 can "switch" off inflammatory white blood cells which has broad implications for the development of new forms of therapy for switching off allergies and autoimmune diseases and for switching on immunity to infections and cancers.
The Role Of IL21 In Integrating Proliferation, Migration And Differentiation Following B Cell Activation.
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Immunity is essential to health and requires the production of antibodies. The best antibodies are made by B-cells coming from specialised structures, called germinal centres (GC). To understand why sometimes immunity is excellent - childhood vaccines - and other times not - HIV infection, aged people - we need to understand what happens inside GC. Our prediction is that by understanding GC B cell behaviour, we will resolve good from poor immune responses and thereby develop improvements.
Immunoglobulin Germline Genes, BCR Repertoire Development And Disease Susceptibility. An Investigation Of Haplotypic Variation Between Individuals
Funder
National Health and Medical Research Council
Funding Amount
$519,828.00
Summary
The immune system is capable of making a repertoire of protective antibodies including literally tens of millions of different specificities. These are produced by permutations and combinations of a small set of ‘germline’ genes. This project will analyse how individual variations in the germline genes lead to individual differences in the repertoires of available antibodies, and will investigate whether or not such differences contribute to our susceptibility to infection and autoimmune disease ....The immune system is capable of making a repertoire of protective antibodies including literally tens of millions of different specificities. These are produced by permutations and combinations of a small set of ‘germline’ genes. This project will analyse how individual variations in the germline genes lead to individual differences in the repertoires of available antibodies, and will investigate whether or not such differences contribute to our susceptibility to infection and autoimmune diseases.Read moreRead less
Our bodies rely on the production of potent, or ‘high affinity’, antibodies to fight infection. We have found that antibody responses are unexpectedly boosted following the depletion of a specific subset of immune cells. This is especially true for B cells that are poor antibody producers. Our findings are likely to be relevant to (1) the design of vaccines to infectious agents that have important CTL and antibody components (e.g. HIV), (2) for the improved production of antibody for therapeutic ....Our bodies rely on the production of potent, or ‘high affinity’, antibodies to fight infection. We have found that antibody responses are unexpectedly boosted following the depletion of a specific subset of immune cells. This is especially true for B cells that are poor antibody producers. Our findings are likely to be relevant to (1) the design of vaccines to infectious agents that have important CTL and antibody components (e.g. HIV), (2) for the improved production of antibody for therapeutic use (e.g. cancer).Read moreRead less
Signal Integration During The Early B Cell/CD4+ T Cell Interactions In T-dependent Antibody Responses
Funder
National Health and Medical Research Council
Funding Amount
$128,783.00
Summary
Effective humoral immunity results from the complex interaction of B and T lymphocytes. STAT3, CD40L, SAP and ICOS are molecules that are involved in this interaction. Genetic mutations of these molecules result in well defined primary immunodeficiencies underscoring their importance. This study aims to characterise the integration of these early signals as well as other inputs that B cells receive and characterise the CD4+ cells that provide this help.