UBC Reports | Vol. 46 | No. 16 | Oct. 19, 2000
Gene can predict disease’s progression and severity
A collaborative research team that includes a recent UBC graduate
and members of the Faculty of Medicine has discovered a gene that
predicts the severity of rheumatoid arthritis (RA).
“This research discovery is a very important breakthrough in the
understanding of rheumatoid arthritis,” says Abbas Khani-Hanjani
of the Immunology Laboratory at Vancouver General Hospital (VGH).
He undertook the research as his doctoral thesis in the Experimental
Medicine Program at UBC.
“We believe the gene identified operates by controlling the degree
of joint inflammation. It is the most powerful indicator currently
recognized for predicting the severity of RA,” he says.
Dr. Paul Keown, a professor of Nephrology and director of the VGH
Immunology Laboratory supervised the research, which started in
1995 and was recently published in the prestigious medical journal,
The Lancet.
The study analysed blood samples of 137 B.C. patients: 48 with
very severe RA unresponsive to all other therapies; 39 with mild
symptoms; and 50 random samples used as a control comparison.
Dr. Diane Lacaille, an assistant professor of Rheumatology and
associate professor of Rheumatology Dr. Andrew Chalmers, reviewed
the patients to ensure they represented either mild or severe disease.
Khani-Hanjani then analysed the blood’s genetic makeup. Research
focused on the interferon gamma gene, which is important in helping
to control the immune system.
Results showed that differences within the gene — called a gene
marker — appear to predict the progression and the severity of RA.
The study shows that different forms of the gene are found in people
with mild or with severe arthritis.
“This discovery promises a simple genetic test to predict risk
of progression and the opportunity to design new drugs to control
the ravages of this disease,” says Keown. “It means we can choose
treatment according to the risk of each patient and can select appropriate
treatment before joint damage has occurred,” adds Lacaille.
Researchers believe that RA is a disorder in the body’s immune
system, causing it to attack the lining of the joints which results
in inflammation and joint damage. The damage becomes worse as the
immune attack continues and results in destruction of cartilage,
bone, tendons and ligaments that can lead to permanent deformity
and disability.
Patients predicted to have mild forms of the disease might be spared
the serious side effects of medications for severe RA, says Chalmers.
In addition, scientists may be able to turn off production of the
gene as a means of treatment.
A chronic disease, RA affects about one per cent of the population.
Onset occurs at all ages but most commonly appears between the ages
of 25 and 50 and affects women three times more often than men.
Researchers are now planning to study about 600 patients in almost
50 centres across North America to confirm and extend the findings
and to use the predictor to determine the most effective forms of
therapy in various stages of the disease.
Other researchers involved in the study are clinical professors
of Pathology and Laboratory Medicine David Hoar from the VGH Immunology
Laboratory and Dr. Doug Horsman from BC Cancer Agency (BCCA); research
technician Michelle Anderson of BCCA; and Rob Balshaw, Dept. of
Mathematics and Statistics, Simon Fraser University.
The research was funded by the Immunology Laboratory of VGH, The
Arthritis Society of Canada, and Novartis Pharmaceuticals, Canada,
Inc.
