(Arthritis & Rheumatism) -- Characterized by inflammation and joint damage, rheumatoid arthritis (RA) is a serious and painful form of arthritis caused by the dysfunction of the immune system. Researchers have long traced the cause of the disease to the body's T cells, an important type of cells that regulates immunity. Various T-cell targeted therapies have been used with limited success.

Recently, a group of researchers set out to explore a dramatically different approach to treating RA. Based in London, led by Professor Jonathan Edwards and Dr. Geraldine Cambridge, with support from the Arthritis Research Campaign of the United Kingdom, the researchers shifted the focus from T cells to B cells - the cells that make antibodies. In the August 2003 issue of Arthritis & Rheumatism, Dr. Cambridge and her team share the results of their new laboratory studies, which shed new light on the role of B cells in RA, as well as raising questions about B cells and autoimmunity.

Twenty-two patients with active RA agreed to an experimental course of B-cell depletion therapy, using rituximab - a drug approved and widely used for treating lymphoma. Of the participants, 20 were female and two were male, the average age was 58, and the mean duration of the disease was 18 years. Upon entering the study, all participants stopped taking disease-modifying antirheumatic drugs (DMARDs), but continued to receive analgesics to alleviate pain as needed. The subjects were divided into five groups, with a range of doses of rituximab by infusion, over a two to four week period. To monitor antibody levels, participants were given blood tests prior to treatment, monthly for the first 6 months after treatment, and then every two to three months for the next two years. Throughout the study and the duration of follow up, all participants were also regularly evaluated for changes in the progression of their RA.

Consistent with the team's previous clinical report the majority of patients showed a marked clinical improvement after treatment with rituximab. Better results were seen with higher dosage treatments. Although the time of disease relapse ranged widely among the subjects, it closely related to the rise in the level of at least one autoantibody - an indicating sign of an immune system breakdown. "The exact degree of B lymphocyte depletion achieved in the solid lymphoid tissues in our patients remains unknown," Dr. Cambridge acknowledges. "There is also no information on what might happen to surviving B lymphocytes and to plasma cells during a period of B lymphocyte depletion."

Despite uncertainty in the long-term effects of this therapy, this study focuses attention on B cells, as a major factor in the cause of RA. Perhaps most importantly, it prompts researchers to further explore the complex role B cells play in our immune system and its many diseases.