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Unusual RAGE protein worsens rheumatoid arthritis

Why does rheumatoid arthritis cripple some while others are only mildly affected? New research from a Columbia University Health Sciences researcher reveals that a certain form of a gene called RAGE is more common in people with rheumatoid arthritis.

RAGE (the receptor for advanced glycation end products) is a protein found on cell surfaces in joints. The binding of RAGE to other proteins called S100/calgranulins leads to inflammation and ultimately joint destruction. In a study, led by Dr. Ann Marie Schmidt, Chief, Division of Surgical Science in the Department of Surgery, the researchers found that the protein product from a certain form of the RAGE gene bound more avidly to S100/calgranulins and increased activity of molecules that led to joint destruction. When RAGE was prevented from binding to the S100/calgranulins arthritic mice had decreased joint inflammation. The findings, published in the May Genes and Immunity, suggest new types of rheumatoid arthritis treatments against RAGE proteins could be developed.