Initiation And Diversification Of Systemic Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$200,749.00
Summary
One of the striking findings in autoimmune diseases such as systemic lupus erythematosus and Sjogren's syndrome is the presence in the blood of autoantibodies reacting with certain proteins or autoantigens. The best known autoantigens are termed La and Ro and are important diagnostic markers in these two common conditions. It appears that the immune response starts against Ro and then spreads to La over time, a process known as epitope spreading. There is emerging evidence in Sjogren's syndrome ....One of the striking findings in autoimmune diseases such as systemic lupus erythematosus and Sjogren's syndrome is the presence in the blood of autoantibodies reacting with certain proteins or autoantigens. The best known autoantigens are termed La and Ro and are important diagnostic markers in these two common conditions. It appears that the immune response starts against Ro and then spreads to La over time, a process known as epitope spreading. There is emerging evidence in Sjogren's syndrome that the severity of this condition is related to the degree of epitope spreading to Ro and La, which in turn is controlled by the genetic background of the individual. We therefore wish to study the initiation of the autoimmune response to Ro and the factors which influence spreading or diversification to La, using a mouse model of La-Ro autoimmunity which we have developed. In addition, we shall investigate the potential role of a recently identified gene in a large group of patients with Sjogren's syndrome. We believe this gene may control the epitope spreading and expression of disease. The role of other molecules called chaperones (which bind to Ro) and complement (involved in clearing dead cells which may trigger autoimmunity) will also be studied. The ultimate goal of the work is to develop ways of blocking the epitope spreading which should ameliorate the disase and patients' symtpoms.Read moreRead less
Sjogren's Syndrome As A Disorder Of Anti-receptor Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
A new approach to understanding Sjogren's syndrome Sjogren's syndrome (SS) is a frequent cause of illness predominantly in women, leading to frequent attendances to medical, dental and allied health practitioners. Historically considered a rarity, SS, in both its primary and secondary forms, is arguably the commonest manifestation of human systemic autoimmunity. Increasingly recognised by clinicians as the unifying diagnosis underlying a plethora of chronic disabling symptoms in women from the f ....A new approach to understanding Sjogren's syndrome Sjogren's syndrome (SS) is a frequent cause of illness predominantly in women, leading to frequent attendances to medical, dental and allied health practitioners. Historically considered a rarity, SS, in both its primary and secondary forms, is arguably the commonest manifestation of human systemic autoimmunity. Increasingly recognised by clinicians as the unifying diagnosis underlying a plethora of chronic disabling symptoms in women from the fourth decade and beyond, therapeutic options remain limited due to our primitive understanding of its cause. Emerging evidence suggests that rather than a consequence of physical destruction of salivary and tear glands by cells of the immune system, severe dryness of the mouth and eyes in SS might be caused by antibodies which block the transmission of signals from tiny nerves to receptors in these glands. We also have evidence that other symptoms experienced by patients with SS, including abnormal sweating, irritable bladder and bowel, and Raynaud's phenomenon, may also be the consequence of blockage of nerve supply. Furthermore, we have detected these blocking antibodies in patients with both primary SS and rheumatoid arthritis accompanied by secondary SS, pointing for the first time to a common underlying cause for SS in these two settings. We propose a new approach to understanding Sjogren's syndrome, as a disease of anti-receptor autoimmunity, akin to Graves disease of the thyroid gland. This opens up exciting possibilities for the development of new techniques for the diagnosis and treatment of SS.Read moreRead less