Researchers at Brigham and Women’s Hospital (BWH) and Harvard Medical School (HMS) have shown that certain types of naturally occurring carbohydrates in the body may cause rheumatoid arthritis, a debilitating, painful disease affecting hundreds of millions of people worldwide.
Although there have been promising advances in treating the symptoms of arthritis, the exact causes of arthritic inflammation, swelling, and destruction of the joints has remained elusive. Now, researchers at BWH have for the first time associated carbohydrates present naturally in the body with this disease.
Dr. Julia Ying Wang, the lead BWH researcher in the study, and an Assistant Professor of Medicine at HMS, has extensively examined the role of carbohydrates in diseases and infections. Her findings were presented at the American Chemical Society’s national meeting.
Wang began wondering whether a particular class of carbohydrates, known as glycosaminoglycans (GAGs), triggered an immune response in the body. GAGs are naturally present as a major component of joint cartilage, joint fluid, connective tissue, and skin. In collaboration with Michael H. Roehrl, M.D., from HMS, Wang studied the effects GAGs had on mice, who subsequently experienced arthritic symptoms, including swelling, inflammation, and joint damage.
“This study shows that rheumatoid arthritis may result from the body’s mishandling of its own carbohydrates that, under normal circumstances, would not be interpreted as a threat,” said Wang. “We found that inflammatory cells that accumulate in arthritic joints attach themselves directly to the glycosaminoglycans. This accumulation of cells leads to painful inflammation and swelling in the affected tissue.”
In addition to their work with mice, Wang and Roehrl also examined human tissue taken from arthritis patients. They discovered the same type of glycosaminoglycan-binding cells in the human tissue. This is the first direct demonstration of such cells in humans and animals.
“It leads us to believe that rheumatoid arthritis may be an unusual immune response,” added Wang.
Given her findings, Wang said subsequent research would most likely focus on the development of drugs aimed at stopping the growth, expansion, or adhesion of immune cells that react to glycosaminoglycans. Wang will continue to investigate carbohydrates and how they affect the body’s immune system.
“This research is extremely promising,” said John Mekalanos, Professor and Chairman of Microbiology and Molecular Genetics at HMS. “This study also suggests plausible models for how bacterial infection might trigger arthritis and how we might go about reversing this debilitating conditions with new therapies.” Mekalanos added, “We are clearly a step closer to understanding the causes of a disease that has left the medical community with unanswered questions and many patients with discomfort and pain.”