UBC Reports | Vol. 46 | No. 16 | Oct. 19, 2000

Discovery holds promise for sufferers of arthritis

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.