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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.

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Figure 1: Schematic illustration of the etiological hypothesis for P. gingivalis and citrullinated α-enolase involvement in RA.
Figure 2: P. gingivalis and citrullination.
Figure 3: Citrullinated proteins are present in the gingiva of a patient with periodontitis.

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Acknowledgements

We thank Professor A. P. Nicholas of the University of Alabama at Birmingham, USA, for the kind donation of the F95 IgM mouse monoclonal anticitrulline antibody.

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All authors contributed equally to researching data for the article, providing a substantial contribution to discussions of the content, writing the article, and to review and/or editing of the manuscript before submission.

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Correspondence to Patrick J. Venables.

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The authors declare no competing financial interests.

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Lundberg, K., Wegner, N., Yucel-Lindberg, T. et al. Periodontitis in RA—the citrullinated enolase connection. Nat Rev Rheumatol 6, 727–730 (2010). https://doi.org/10.1038/nrrheum.2010.139

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