Fibrin Looks to Play Role in Development of RA

In November 2007, researchers at Cincinnati Children's Hospital released the first study showing that a protein called fibrin, one normally involved in blood clotting, also plays an important role in the inflammatory response and development of rheumatoid arthritis. The study's lead author was Jay Degen, Ph.D., a researcher in Developmental Biology at Cincinnati Children's Hospital, and the results of the study were published in the November issue of The Journal of Clinical Investigation.

Although rheumatoid arthritis's precise cause is not fully known, activation of specific components in the body's immune system seem to play a major role in its onset and early progression. Fibrin deposits are a prominent feature of arthritic joints and the protein appears to be a link between systems that control inflammation and bleeding within joints. Specifically, the disease seems to be driven by the engagement of inflammatory cells with the mesh-like matrices formed by fibrin to create blood clots at the integrin receptor, aMB2.

The study was conducted by a team that includes researchers from Cincinnati Children's Hospital and the University of Cincinnati's College of Medicine using genetically-engineered mice with collagen-induced arthritis of the knee and paw. The mice were designed to have selective alterations in the production of fibrinogen, a precursor to fibrin, to allow researchers to evaluate the inflammatory impact of fibrin, especially as it interacts with aMB2.

The researchers reported that the study clearly establishes that fibrin is a powerful, although context dependent, determinant of inflammatory joint disease. In addition, the findings also suggest that pharmacologically interrupting the interaction of fibrin and aMB2 might be effective in treating arthritic disease, as well as many other inflammatory diseases. The researchers suggest that future therapies should be designed to interrupt these localized interactions of inflammatory cells and fibrin.

Article References
Blood Clotting Protein Linked To Rheumatoid Arthritis, site accessed on 11/19/07