Two Proteins Linked to Rheumatoid Arthritis

Two Proteins Linked to Rheumatoid Arthritis

Two protein molecules appear to play a key role in the development of rheumatoid arthritis, according to researchers at the University of Illinois at Chicago College of Medicine, who found high levels of the proteins in the joints of patients affected by the disease.

The findings, which are being reported in the journal Annals of the Rheumatic Disease, could lead to new therapies for treating rheumatoid arthritis.

“Our results show, for the first time, that these two proteins – a receptor and its corresponding binding protein – play a key role in the progression of rheumatoid arthritis pathology,” said Shiva Shahrara, an associate professor of rheumatology at UIC.

220px-RheumatoideArthritisAPRheumatoid arthritis (RA) is a chronic autoimmune disease in which the body’s own defenses attack the tissues lining the joints, causing painful swelling, inflammation and bone erosion. As the disease progresses, many RA patients become significantly disabled. About 1.5 million Americans and 1% of adults worldwide suffer from RA.

One of the hallmarks of rheumatoid arthritis is the development of new blood vessels, or angiogenesis, in the joints.

“The swelling of joints is caused by the abnormal migration of a variety of different cell types into the joint,” Shahrara said. “And as these cells accumulate, they need to be supplied with oxygen and nutrients, and so angiogenesis accompanies the joint swelling.”

A protein called CCL28 is often found in the body under low oxygen conditions, or hypoxia. Joints affected by rheumatoid arthritis can also become hypoxic, so the researchers wanted to see if the protein and its receptor could be found in the joints of RA patients.

The researchers measured the levels of the proteins in joint tissues and fluid from patients with rheumatoid arthritis and osteoarthritis, a more common joint inflammation caused by physical wear and tear. Patients of both types had protein levels that were significantly higher than individuals without joint disease.

The research team also found that CCL28 attracts the surface-lining cells that carry its receptor. When they added CCL28 to cells carrying the receptor, the cells organized into new blood vessels. But if they chemically blocked the receptor and added CCL28, the formation of blood vessels was reduced.

The finding, according to Shahrara, provides “strong evidence” that the binding of CCL28 to joint-lining cells carrying its receptor is a necessary step in angiogenesis.

The growth of new blood vessels is a normal process in tissue growth and development, as well as in wound healing. However, angiogenesis also plays a significant role in the growth of malignant tumors.

This research was funded by the National Institutes of Health, the U.S. Department of Defense, the American College of Rheumatology and the Arthritis Foundation.

Authored by: Pat Anson, Editor