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 The single Thymine-Guanine base substitution in the Roquin gene that causes autoimmune disease in carriers
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Bits & pieces |
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The name Roquin comes from San Roque, the patron saint of bubonic plague victims. The lupus-suffering 'sanroque' mice have swollen lymph glands that resemble the swellings caused by bubonic plague
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Lupus attacks many tissues and organs, including the joints, kidneys, heart, lungs, blood, and skin. The disease is most common amongst women of childbearing age, affecting one in 700 women in that age group
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In type one diabetes, the immune system attacks insulin producing cells in the pancreas. Insulin regulates blood sugar levels, and sufferers must inject the hormone to keep their blood sugar at normal concentrations.
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Roquin roll medicine |
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| Incredibly adaptable and sporting a lethal array of molecular weaponry, the immune system is the body's front line of defence against disease-causing invaders such as bacteria, viruses and parasites. |
However, sometimes this formidable defender can turn against us - mistakenly attacking and damaging the body's own tissues. This case of mistaken identity is the cause of common autoimmune diseases such as type one diabetes, rheumatoid arthritis and lupus.
Thanks to a new gene discovery by immunologists at The John Curtin School of Medical Research at The Australian National University, the secrets of autoimmune disease are one step closer to being revealed.
By screening mice for the self-reactive antibodies that cause lupus, the research team was able to work backwards to discover the type of mutation responsible. They discovered a single point mutation in the previously unknown Roquin gene was causing the lupus symptoms.
The symptoms of lupus are many and complicated: they include swollen lymph nodes, inflamed joints, rashes, kidney problems and anaemia.
The finding that a single mutation could cause such a complex set of symptoms is one of the exciting things to emerge from the research, explained clinical immunologist and Roquin researcher Dr Matthew Cook.
"One of the significant results from this find, a really striking result, is that we're looking for phenotypes which come about from one single genetic abnormality" said Matthew. "And we've got this complex phenotype, the lupus phenotype, which has been induced by one change in one gene - the Roquin gene."
The Roquin gene plays a vital role in preventing the immune system from attacking friendly cells. It suppresses the production of antibodies that target the body's tissues, to keep us safe from our own molecular weaponry.
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Dr Carola Vinuesa and
Dr Matthew Cook
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Antibodies are proteins normally produced by the body in response to infection or immunisation. They bind to pathogens, neutralising them or preparing them for destruction by other immune cells.
B-cells are the antibody factories of the immune system. When they recognise a potential pathogen they begin to multiply and produce antibodies to bind to their target. To do this however, they need assistance from helper T-cells that have also recognised the same potential pathogen.
Roquin specifically stops self-reactive T-cells from providing this assistance to B-cells, preventing the production of antibodies that might target healthy tissue. T-cells that react to invading pathogens are not suppressed by Roquin, allowing the immune system to mount a powerful defence against foreign threats without accidentally attacking friendly cells.
When a mutation causes Roquin to stop working, the immune system loses one of its safeguards against autoimmune diseases like lupus and diabetes. This previously unknown pathway has already suggested new areas for study, said head researcher Dr Carola Vinuesa.
"Roquin is part of a new pathway, and we still don't know which are the proteins that interact with Roquin" explained Carola.
"What we are doing at the moment is trying to identify these other molecular blocks that act together with Roquin. These might be linked to a bigger pathway, and potential new candidates that might be good drug targets in a treatment of lupus."
The gene also has implications for diabetes research, as the researchers found Roquin defects can cause type one diabetes in mice. They are now sequencing the gene in diabetes patients, to determine whether a similar defect causes the disease in humans.
All of this is good news for autoimmune sufferers, improving prospects for more selective treatments in the future.
"An advance like this gives us potential for targeting these pathways more specifically rather than just blocking the whole function of T-cells, which is basically what current treatments are doing" said Carola. "So, it offers some hope."
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