Rheumatoid Arthritis: Improving prognosis

He Kitenga, 2005

Dr Paul Hessian hopes his team’s studies of rheumatoid arthritis inflammation may eventually enable doctors to offer patients in the early stages of this disease a more accurate prognosis – and more efficient treatment.

“We can diagnose rheumatoid arthritis reasonably accurately,” says Hessian, a senior research fellow in the Department of Physiology. “ There have been significant advances in the last few years, so now we need to improve our ability to determine prognosis.”

Rheumatoid arthritis (RA) varies in its severity. Some patients may have mild pain and inflammation that never develop into anything worse. In others, the disease progresses to involve several joints and other parts of the body. In its worst form, it can destroy joints over a matter of months, crippling hands, feet and toes.

Most people with early stages of RA present with sore hands. “The challenge is to distinguish those who will go on to have rapid destruction of joints from those who will just have joint pain due to inflammation, but no severe destruction,” says Hessian.

“The treatments you could offer them would be quite different. We do have effective anti-inflammatory agents available – although some are not in New Zealand yet – and new biological reagents are coming out of research into inflammation. So how do you predict what course the disease will take so you can treat it in its early stages?”

Hessian and fellow researcher Associate Professor John Highton (Medical and Surgical Sciences) have received a $900,000 grant to try to answer that question.

They have been looking at inflammatory cells in the synovial membrane of rheumatoid joints. “Different types of white blood cells come out of the blood and into the synovial tissue in response to inflammation,” says Hessian. “They group together in clusters to increase their efficiency. We think one of these types of cluster – lymphoid follicles – may be connected with the milder form of the disease. If we can support this and identify their presence early on, we may be able to offer some patients a good prognosis and treat them accordingly.”

Lymphoid follicles are normally found in lymph glands and the spleen, but detecting them in joints is not easy. Their formation depends on follicular dendritic cells, which themselves are difficult to find. Now researchers are working at the molecular level to trace follicular dendritic cells.

“If we can identify genes associated with follicular dendritic cells, we should be able to determine if they are there,” says Hessian. “We don’t need to see the cells themselves.”

The research team is working with tissues from joint replacements, and with an extensive collection of rheumatoid arthritis biopsies taken by a collaborator from Adelaide Repatriation General Hospital, Professor Malcolm Smith, who was a William Evans Fellow at Otago in 2004.

“The biopsy collection is unsurpassed internationally and provides an outstanding opportunity to pursue an avenue of research not available to others,” says Hessian.

“We’ll be able to match the clinical records for those patients with biopsies from the early stages of RA through several years, so we can start to correlate our ideas. If we get a successful treatment, what is changing in the biopsies? Do we see the growth of follicles? We should be able to see what treatments succeed, and match them with a much earlier and more accurate prognosis for patients.”