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Research Offers Treatment Hope for Ankylosing Spondylitis

By Bob Ewing     Oct 21, 2007 in Health
Research funded by the Wellcome Trust and the Arthritis Research Campaign has identified two genes implicated in the disease ankylosing spondylitis, a common disease causing primarily back pain and progressive stiffness.
A research team led by Professors Lon Cardon, Matthew Brown and Paul Wordsworth - from the Wellcome Trust Centre for Human Genetics at the University of Oxford have analyzed DNA samples from 1000 patients with ankylosing spondylitis and a further 1500 people unaffected by the disease in search of genetic mutations which, if present, increase a person's risk of developing the disease.
The team identified two genes which are implicated in the ankylosing spondylitis which is a common disease that causes primarily back pain and progressive stiffness.
The research was published online in Nature Genetics and was funded by Wellcome Trust and the Arthritis Research Campaign.
Ankylosing spondylitis mainly affects the spine but can also affect other joints, ligaments and tendons. It can also, but more rarely, affect as the eyes, lungs, bowel and heart.
The team used a technique that is known as genome-wide association scanning, to conduct their analysis. The study’s findings were then confirmed by a team at University of Texas (Houston) led by Professor John Reveille.
"Ankylosing spondylitis is a painful and often very disabling disease," says Professor Brown. "Yet, our understanding of the causes of the disease, and hence our ability to treat it effectively, is relatively poor."
The two genes that the team identified are ARTS1 and IL23R, which increase the risk of developing the disease. There are now three genes that have been identified as being involved with this disease with the genetic variant HLA-B27 being the third.
If someone is carrying all three variants they have a 1 in 4 chance of developing the disease.
It is already known that the IL23R gene plays a role in the immune response to infection, providing instructions for making a receptor present on the surface of several types of immune system cells.
The receptor triggers certain chemical signals that are inside the cell that promote inflammation and help coordinate the immune system's response to infection.
This receptor is already recognized as playing a role in a number of autoimmune diseases, such as Crohn's disease (a type of inflammatory bowel disease) and psoriasis (a skin disease).
Ankylosing spondylitis, Crohn's disease and psoriasis have been known occur together, and this genetic finding goes a long way to explain why.
"We already know that IL23R is involved in inflammation, but no one had ever thought it was involved in ankylosing spondylitis," says Professor Brown. "A treatment for Crohn's disease that inhibits the activity of this gene is already undergoing human trials. This looks very promising as a potential treatment for ankylosing spondylitis."
For the past 37 years, scientists have known that there is a genetic component to ankylosing spondylitis. This is when the gene HLA-B27 was discovered it was not known how this gene led to disease, now Professor Brown believes that the gene ARTS1 may hold the answer.
It is a protein that is created by the HLA-B27 gene that takes fragments of pathogens and displays them on the outside of immune cells; then the fragments trigger the immune system to fight against the pathogen.
ARTS1 is involved in breaking up the pathogen into 'bite-size chunks' that can be displayed by HLA-B27.
"This strongly suggests that in ankylosing spondylitis, there are problems with the information that the HLA-B27 protein receives, thereby causing the disease," says Professor Brown.
"These findings are very exciting and show the value of exploring the genetics of disease," says Dr Mark Walport, Director of the Wellcome Trust. "It usually takes many years between genetic discoveries and new treatments for disease. In this case the two genes discovered to be associated with ankylosing spondylitis provide striking insights into the mechanisms of the disease and offer a possible new pathway for treatment."
"These genetic studies involve large patient samples and require expertise over a wide range of scientific specialties", says Professor Cardon. "Bringing together these two consortia was the final key that enabled these exciting discoveries."
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