If the test comes back positive for the human leukocyte antigen B27 (HLA-B27), the patient’s likelihood of having AS increases. But, no one seems to know exactly why.
An international team of researchers from The University of Texas Health Science Center at Houston (UTHealth) Medical School and other institutions believe they may be on the road to solving this mystery. Findings of their new genetic study are online ahead of the August print issue of Nature Genetics.
Research by UTHealth prof John Reveille, M.D., and others sheds new light on ankylosing spondylitis.
“We have evidence of a gene-gene interaction that gives us a potential mechanism by which HLA-B27 may cause ankylosing spondylitis,” said John D. Reveille, M.D., study co-author and director of the Division of Rheumatology and Clinical Immunogenetics at the UTHealth Medical School.
Ankylosing spondylitis and its related diseases involve up to 2.4 million people in the United States. The disease triggers inflammation in joints, particularly the spine and pelvis. In severe cases, it creates a forward-stooped posture. The late Pope John Paul II is widely thought to have had ankylosing spondylitis as is Pharaoh Ramses II, Reveille said.
The Spondylitis Association of America reports that more than 95 percent of Caucasians with AS have HLA-B27. But, people do not have to be HLA-B27 positive to have AS and the majority of those with HLA-B27 do not develop the disease. The link between AS and HLA-B27 varies between ethnic groups.
The study led by Reveille and Matthew Brown, M.D., of the University of Queensland reported a link between a gene producing protein, ERAP1, and HLA-B27. For example, ERAP1 was associated with ankylosing spondylitis in HLA-B27 positive patients; whereas, there was no association between ERAP1 and AS in HLA-B27 negative patients.
Stephen Haskew, who has AS and is a co-leader of a support group at the UTHealth Medical School, called the discovery a “significant finding.” He said that learning more about the mechanisms involved in the disease could aid in the development of new treatments.
The HLA-B27 protein is found on the surface of white blood cells and can impact the ability of the immune system to fight off infections. Both HLA-B27 and ERAP1 work together inside cells to combat infection.
Other indications of AS include a history of AS in the family and frequent gastrointestinal issues. While doctors can manage the symptoms, there is currently no cure for ankylosing spondylitis.
Findings were based on an analysis of the DNA of almost 7,000 people with ankylosing spondylitis. The analysis also led to a genetic variant that could aid in the development of a less expensive blood test for HLA-B27.
Haskew added, “If you could reduce the cost of the test, you may be able to increase the number of people getting tested, which would lead to an earlier diagnosis.”
In addition, the genetic analysis led to the identification of three genetic variants strongly associated with the disease.
Reveille said genetic research is helping efforts to find a cure. As an example of a current treatment tied to genetic research, he pointed to biologic medications, also known as Tumor-Necrosis-Factor alpha (TNF-a) blockers, that can potentially slow or halt disease progression in some people. Research on TNF-a was done at UTHealth Medical School and Memorial Hermann-Texas Medical Center.
The most recent study involved the Australo-Anglo-American Spondyloarthritis Consortium, which is led by Reveille in collaboration with the Wellcome Trust Case Control Consortium 2. Findings were replicated in an independent cohort from Australia, Great Britain and The Spondyloarthritis Research Consortium of Canada.
Stephen Haskew helps lead a support group for people with ankylosing spondylitis (AS) at the UTHealth Medical School. From left to right are: Haskew, his wife, Eleanor and their daughters, Aimee and Kate. Kate also has AS.
The study is titled “Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility.”
Reveille is a professor of medicine, Linda and Ronny Finger Foundation Distinguished Chair in Neuroimmunologic Disorders, the George S. Bruce, Jr. Professor in Arthritis & Other Rheumatic Diseases at the UTHealth Medical School, as well as chief of rheumatology at Memorial Hermann-TMC. He is the director of The Frank C. Arnett M.D., Center for Autoimmunity and Immunobiology in the UT Professional Building, 6410 Fannin, Suite 450; 713-486-3100.
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