Citrullination as a plausible link to periodontitis, rheumatoid arthritis, atherosclerosis and Alzheimer’s disease

Abstract

Periodontitis, rheumatoid arthritis (RA), atherosclerosis (AS) and Alzheimer’s disease (AD) are examples of complex human diseases with chronic inflammatory components in their etiologies. The initial trigger of inflammation that progresses to these diseases remains unresolved. Porphyromonas gingivalis, is unique in its ability to secrete the P. gingivalis-derived peptidyl arginine deiminase (PPAD) and consequently offers a plausible and exclusive link to these diseases through enzymatic conversion of arginine to citrulline. Citrullination is a post-translational enzymatic modification of arginine residues in proteins formed as part of normal physiological processes. However, PPAD has the potential to modify self (bacterial) and host proteins by deimination of arginine amino acid residues, preferentially at the C-terminus. Migration of P. gingivalis and/or its secreted PPAD into the bloodstream opens up the possibility that this enzyme will citrullinate proteins at disparate body sites. Citrullination is associated with the pathogenesis of multifactorial diseases like RA and AD, which have an elusive external perpetrator as they show epidemiological associations with periodontitis. Therefore and PPAD deserves some prominence as an external antigen, in at least, a subset of RA and AD cases, with as yet unidentified, immune/genetic vulnerabilities.