Citrullinated collagens in the pathogenesis of rheumatoid arthritis

Abstract

Citrulline formation through the deimination of arginine residues has recently been identified as an enzymatic post-translational modification of proteins that could be related to breaking the tolerance to self-antigens in the development of rheumatoid arthritis. Autoantibodies recognizing citrullinated peptides are highly specific indicators of early rheumatoid arthritis. However, current knowledge of the natural proteins that are citrullinated does not explain the main manifestations of the disease, that is, progressive damage to cartilage and bone – tissues rich in extracellular matrix. Several collagen types are present in the joint, where they provide the structural scaffold of the tissues. Recent findings indicate that both the ubiquitous Type I collagen and the cartilage-specific Type II collagen can be enzymatically citrullinated in vitro. Synthetic citrullinated peptides related to collagen sequences can be used as antigens. Autoantibodies to these citrullinated forms are found in patients with early rheumatoid arthritis. This review summarizes what is known regarding the occurrence of citrulline in a major class of extracellular matrix proteins, the fibrillar collagens and the significance of autoantibodies to citrulline in these proteins.

Keywords::

• autoantibody
• citrullination
• collagen
• extracellular matrix
• rheumatoid arthritis