Genetic disease gives insight into how the body responds to infection
14th December 2006
Research into a rare genetic condition called Aicardi Goutières Syndrome (AGS) has unexpectedly shed new light on how the body responds to viral infections. It may have also revealed some of the processes involved in autoimmune diseases like lupus.
CT brain scans showing the similar calcification and brain damage in AGS(left) and congenital viral infection (right). The bright white areas in the centre of the brain are calcification. Right hand figure copyright: Lippincott Williams & Wilkins.
Babies affected with AGS have problems closely resembling those caused by viral infections such as rubella and cytomegalovirus when the baby is infected during pregnancy. However, AGS is caused by abnormal genes rather than a virus.
In collaboration with scientists at the University of Leeds, Dr Andrew Jackson of the Medical Research Council Human Genetics Unit in Edinburgh has helped to identify four of the genes that cause AGS.
These genes give instructions to make two enzymes called nucleases. The collaboration discovered that it is the absence of these nucleases in AGS that triggers symptoms similar to those of viral infection acquired in the womb.
During the normal life-cycle of our cells, nucleases break down naturally produced ‘waste’ DNA and RNA. In AGS, the lack of nucleases is likely to lead to a build up of such DNA and RNA molecules. This DNA/RNA may then initiate an immune response following similar pathways to that mounted against viral DNA and RNA. This is likely to explain why AGS mimics viral infection, and how viral infections in pregnancy cause damage to the brain.
This immune response mechanism is also likely to play a role in causing other autoimmune diseases, such as lupus. Dr Andrew Jackson of the MRC Human Genetics Unit explains:
"Nucleases are enzymes that are found in all cells in the body. Their job is to break down DNA and RNA into their component parts. Scientists have long understood how these particular nucleases work, but the discovery of their relationship to innate immune response was unexpected.
The research results suggest that the genes that cause AGS may help us to understand more about the body’s immune response to viruses like rubella and cytomegalovirus. Understanding exactly how the body’s immune system responds to DNA and RNA will help in the long term to identify more effective treatments for viral infections and autoimmune diseases.’’
This research was published in two papers in Nature Genetics in July 2006.
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