A team of researchers from the United States and Japan led by Prof Nirmal Banda from the University of Colorado School of Medicine has found that fat cells in the knee secrete a protein linked to rheumatoid arthritis.

Rheumatoid arthritis is an autoimmune condition that gradually destroys bones, muscles, joints, cartilage and other connective tissue.

Prof Banda explained: “we found that fat in the knee joints secretes a protein called pro-factor D which gives rise to another protein known as factor D that is linked to arthritis. Without factor D, mice cannot get rheumatoid arthritis.”

Factor D is part of the complement system, a complex array of over 40 proteins that help the body fight off bacteria and other pathogens. In studies with arthritic mice, Prof Banda’s team previously found that the complement pathway involving factor D made the mice susceptible to inflammatory arthritis.

In the current study, published online in the Journal of Immunology, the scientists discovered that removing factor D, rather than the entire complement system, achieves the same result without compromising other parts of the system that can fight infection.

“We know that fat is normally present around all organs of the body,” Prof Banda said. “But what we didn’t know until now was that the fat is secreting this protein which actually triggers arthritis in the joints.”

He noted that fat does the same thing in all the joints, not just the knees. That means new medications resulting from this discovery could treat inflammatory arthritis throughout the body.

While it’s theoretically possible to destroy the entire complement system in humans to prevent arthritis, it eventually returns along with a renewed risk of contracting the disease. In the meantime, patients can get infections and other complications because they lack this critical part of the immune system.

“The complement system is both friend and foe,” Prof Banda said. “We believe we can shut down one part of the complement system that triggers disease without shutting down the rest. If so, we will be making a major stride toward treating and perhaps even curing rheumatoid arthritis.”

______

Bibliographic information: William P. Arend et al. Roles of Adipocytes and Fibroblasts in Activation of the Alternative Pathway of Complement in Inflammatory Arthritis in Mice. The Journal of Immunology, published online before print May 6, 2013; doi: 10.4049/jimmunol.1300580