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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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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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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DOI: https://doi.org/10.1038/nrrheum.2010.139
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