Peptidylarginine deiminase type 4, anticitrullinated peptide antibodies, and rheumatoid arthritis.

Anticitrullinated peptide antibodies seem to be one of the most clinically reliable serologic markers for rheumatoid arthritis (RA). A genetic approach revealed that one of the citrullinating enzymes has a RA-susceptible variant. Peptidyl citrullination alters the chemical character of peptides and, subsequently, their antigenicity as well. This change in antigenicity of self-peptides seems to invoke citrulline-related autoimmunity. Although the precise physiologic role of citrullination is still unknown, accumulating data indicate that citrullination has a definite role in biologic phenomena, along with other posttranslational protein modifications, such as methylation and phosphorylation. In RA synovial tissue, two of five PADI isotypes are known to be expressed, and their expression is regulated at multiple steps: transcription, translation, intracellular localization, and activation/inactivation of PADI proteins. Further investigations on citrulline and PADIs from various aspects will provide a more profound understanding of RA-related autoimmunity.