Big news for ankylosing spondylitis sufferers

By Dr. Ananya Mandal, MDJul 12 2011

In a medical breakthrough, researchers from the University of Queensland have found that there is a possible genetic link in a specific painful form of arthritis, which fuses bones in the spine and pelvis.

Researchers at The University of Queensland Diamantina Institute (UQDI) in Brisbane have made a major breakthrough in the understanding of the molecular mechanisms underlying the disease, ankylosing spondylitis (AS). AS causes the immune system to attack the spinal and pelvic joints, leading to chronic inflammation. AS results in bone growth and can consequently cause the spine and or pelvis becomes fused into a fixed position. AS affects up to 80,000 Australians and currently there is no treatment available that causes disease remission.

This new UQDI discovery by researchers at could help pave the way for the development of new treatments. Professor Matt Brown led his team to form an international consortium with research groups in the UK, US and Canada to embark upon the largest study in history into the genetic causes of AS. Their research has identified eight new genes that help clarify previously unexplained aspects of AS. In particular, these genes help explain why bone formation occurs and why some AS patients also develop the conditions Inflammatory Bowel Disease and/or psoriasis.

Professor Matt Brown said the findings shed light on a 40-year-old genetic mystery. He explained that in the 1970s it was discovered that nearly all AS patients carried a particular gene called HLA-B27. He said, “…the link between AS and HLA-B27 is one of the strongest known genetic associations of any common disease. However, the precise role this gene plays in AS has never been clear until now.”

The researchers analyzed DNA from 1,787 people from Britain and Australia who had the condition (cases) and 4,800 controls of European ancestry. They looked at genetic variations across the DNA to determine whether there were differences between people who had the condition and those who didn’t. The researchers combined their findings with the findings of another similar study, the Australo-Anglo-American Spondyloarthritis Consortium, which looked for genetic associations in 3,023 cases and 8,779 controls.

The team found a mutation in a second gene, ERAP1 that only appears in HLA-B27 positive AS patients. The finding suggests these two genes work together in AS to disrupt the way the cells in the spinal and pelvic joints interact with the immune system. This may help in the development of new drugs say researchers.

The study, published this week in the journal Nature Genetics, also has far reaching implications beyond AS. “These crucial findings provide the first confirmation that in humans, as has been shown in plant and other animal species, interaction between genes is important in influencing disease risk,” Professor Brown said.

Professor Peter Donnelly, from the University of Oxford, said, “Thanks to over 5,000 people with ankylosing spondylitis who have provided DNA samples, we were able to undertake the largest study of the genetics of this painful and often disabling disease. It revealed important, and in some cases surprising, new insights into the disease.”

The study was carried out by researchers from The Australo-Anglo-American Spondyloarthritis Consortium and the Wellcome Trust Case Control Consortium 2. Funding was provided by a variety of sources, including Arthritis Research UK, the Wellcome Trust and the Oxford Comprehensive Biomedical Research Centre.

The National Ankylosing Spondylitis Society's director, Debbie Cook, welcomed the findings and said the charity looks forward to further developments in the future.