Periodontitis in RA—the citrullinated enolase connection

Abstract

Autoimmunity in rheumatoid arthritis (RA) is characterized by an antibody response to citrullinated proteins. Two of the risk factors for RA-HLA-DRB1 shared epitope alleles and smoking-are also associated with periodontitis, which is largely, but not exclusively, caused by Porphyromonas gingivalis infection. Furthermore, RA and periodontitis have a similar pathophysiology, characterized by destructive inflammation. The citrullination of proteins by P. gingivalis and the subsequent generation of autoantigens that drive autoimmunity in RA represents a possible causative link between these two diseases. Antibodies directed towards the immunodominant epitope of human citrullinated α-enolase cross-react with a conserved sequence on citrullinated P. gingivalis enolase. On the basis of this cross-reactivity, in this Perspectives article we explore the hypothesis of molecular mimicry in the etiology of RA, with citrullinated enolase as the specific antigen involved.

Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis

“…The fact that Porphyromonas gingivalis (Pg) has enzymatic peptide-citrullinating capacity has led to the hypothesis that, in susceptible individuals, this oral pathogen may evoke a systemic immune response leading to RA (McGraw et al 1999;Rosenstein et al 2004;Mikuls et al 2009;Hitchon et al 2010;Lundberg et al 2010). In the present study, information on oral health status and From previous studies we know that the presence of circulating IgA-ACPA relates to a more aggressive disease (Verpoort et al 2006;Svärd et al 2008;Svärd et al 2010).…”

Periodontal Pathogens Directly Promote Autoimmune Experimental Arthritis by Inducing a TLR2- and IL-1–Driven Th17 Response

“…Citrullination of proteins by P. gingivalis and the subsequent generation of potential autoantigens that drive autoimmunity in RA have been suggested as another possible link between RA and PD (31). A recent study of the complex subgingival microbiota of patients with recent-onset RA, however, found that the presence of P. gingivalis in RA is merely associated with the severity of PD but not with ACPA titers (14).…”

“…Previous studies on the relationship between RA and PD have primarily focused on P. gingivalis, probably because of its ability to citrullinate proteins and generate potential autoantigens (31,32). However, P. gingivalis possesses several other virulence factors such as LPS, fimbriae hemagglutinin, and gingipains as well, which may directly contribute to its pathogenicity regardless of citrullination (33,34).…”

Toll-like Receptor

“…158,159 Oral bacteria, such as prophyromonas gingivalis by molecular mimicry of citrullinated enolase, has been suggested to be involved in triggering of the disease. 160 Apart from such possible combined effect of genetic and environmental factors, there is also increasing awareness that innate immune system could directly contribute to onset and lasting course of RA. High percentage of bacterial DNA was detected in the RA and reactive arthritis patients.…”