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Study Suggests Carbohydrates Are Attacked in Arthritis


NYTimes 08/26/02

Scientists may have discovered an important, unexpected clue in the long, elusive search for the cause of rheumatoid arthritis.

Rheumatoid arthritis, a disease without cure that afflicts more than two million people in the United States, is thought to be caused by out-of-control immune cells that mistakenly attack cartilage and joints.

But scientists have been unsure exactly what in the cartilage and joints the immune cells are attacking.

In such autoimmune diseases, the body's defense system typically turns against itself by homing in on and destroying one of the body's proteins. Some scientists have proposed that rheumatoid arthritis attacks collagen, a fibrous protein in cartilage, bone and connective tissues, but the evidence has been ambiguous.

The new research suggests that the target of destruction is not a protein, but carbohydrates.

"There has to be some sort of attraction," said Dr. Julia Y. Wang, a professor of medicine at Harvard Medical School and Brigham and Women's Hospital in Boston. "Our study for the first time identifies a direct link between carbohydrates in our tissues, the immune system and rheumatoid arthritis."

Dr. Wang and Dr. Michael H. Roehrl of Harvard believe the target is a type of carbohydrate known as glycosaminoglycans, a major component of cartilage, joint fluids, connective tissue and skin.

If true, the findings could lead to drugs that reduce or disarm the rampaging cells.

Dr. Wang presented the findings yesterday at the national meeting of the American Chemical Society in Boston. Other scientists will have to repeat the experiments before the theory gains acceptance.

"I think this is of considerable interest and potentially very important," said Dr. John H. Klippel, medical director of the Arthritis Foundation. "It opens a new way of thinking about this disease. We don't think of the immune system as responding to complex carbohydrates."

In the experiments, Dr. Wang and Dr. Roehrl injected glycosaminoglycans into mice, inducing arthritis-like swelling and inflammation around the animals' joints. "The bones start to erode," Dr. Wang said.

The mice also developed lesions in their tendons and skin, also symptoms of rheumatoid arthritis.

The researchers developed a test to find immune cells that bind to glycosaminoglycans. The test revealed high concentrations of the cells not only in and around the mice's rheumatoid lesions, but also in bone marrow.

Dr. Wang said she believed that the body produces the carbohydrate-binding cells in bone marrow as a normal matter of course to control the level of glycosaminoglycans in the blood. When the level of the carbohydrate soars for some reason, she said, the immune system appears to respond by churning out more immune cells and some of the excess miss their intended targets in the blood and bind to glycosaminoglycans in the joints instead, to disastrous effect.

Tests on joint tissue from nine human arthritis patients showed the immune cells in people suffering from rheumatoid arthritis, but not other forms of arthritis, which are not autoimmune diseases. Dr. Wang said she did not know why the carbohydrate levels might become elevated.

Rheumatoid arthritis accounts for about 2.1 million of the 42 million cases of arthritis in the United States and strikes fairly young in life, usually middle age, but sometimes as early as the 20's and 30's. About three-quarters of patients are women.

Currently, some drugs alleviate the disease's painful swelling, but there is no cure.

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