Is Citrullination the Missing Link between Periodontal Disease and Rheumatoid Arthritis?

Abstract

Connections between periodontitis (PD) and rheumatoid arthritis (RA) are suggested by an increased prevalence of PD in RA, shared environmental and genetic risk factors, and correlating levels of severity when the two diseases occur together. Here, we compare and contrast the results from numerous studies documenting this association, and highlight the involvement of citrullination in the development of autoimmunity leading to the destructive pathology that characterizes RA. The contribution of citrullination to RA may occur in at least three distinct phases: (i) the initial breakdown of tolerance leading to autoimmunity; (ii) the maturation of the citrulline specificity of the autoantibody response; and (iii) the pro-inflammatory effect of citrullinated proteins themselves in established disease. We conclude that citrullination is more than a ‘missing link’; rather, it is an active process in the evolution of low levels of autoimmunity found in PD into the pathogenic anti-citrullinated protein response specific to RA.