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December 14, 2016Science Translational MedicineOpen Access

Aggregatibacter actinomycetemcomitans –induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis

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Authors

MKMaximilian F. KonigHoward Hughes Medical InstituteLALoreto AbuslemeUniversidad de Santiago de ChileJRJesper ReinholdtAarhus University

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Implication

Translational study reveals that Aggregatibacter actinomycetemcomitans induces hypercitrullination via leukotoxin A in periodontitis, suggesting a microbial trigger for rheumatoid arthritis.

Key Points

  • Investigate whether periodontal dysbiosis and specific oral pathogens trigger autoantigen hypercitrullination and initiate autoimmunity in rheumatoid arthritis.
  • Profiled the proteome and microbial composition of gingival crevicular fluid from patients with periodontitis and healthy controls using mass spectrometry.
  • Treated human neutrophils with candidate periodontal pathogens and purified pore-forming leukotoxin A to evaluate citrullinome activation and extracellular trap release.
  • Assessed exposure to leukotoxic bacterial strains, anti-citrullinated protein antibodies, rheumatoid factor, and HLA-DRB1 shared epitope alleles in patients with rheumatoid arthritis.
  • Periodontitis gingival crevicular fluid exhibited an extensive citrullinome that closely mirrored the autoantigen hypercitrullination patterns found in rheumatoid joints.
  • Aggregatibacter actinomycetemcomitans uniquely triggered neutrophil hypercitrullination and the release of citrullinated autoantigens via the pore-forming toxin leukotoxin A.
  • Exposure to leukotoxic Aggregatibacter actinomycetemcomitans in rheumatoid arthritis was significantly associated with autoantibody positivity, which was further restricted by HLA-DRB1 risk alleles.

Cite This Study

Konig et al. (2016) studied this question.

synapsesocial.com/papers/69ff7fe04716aad0cc855ebahttps://doi.org/10.1126/scitranslmed.aaj1921
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Heightened immune response to autocitrullinated Porphyromonas gingivalis peptidylarginine deiminase: a potential mechanism for breaching immunologic tolerance in rheumatoid arthritis2013 · 204 citations
  2. 2Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies.1998 · 1,462 citations
  3. 3Characterization of a new serotype g isolate of Aggregatibacter actinomycetemcomitans2010 · 68 citations
  4. 4Rheumatoid Factor as a Potentiator of Anti–Citrullinated Protein Antibody–Mediated Inflammation in Rheumatoid Arthritis2014 · 243 citations
  5. 5Microbial complexes in subgingival plaque1998 · 5,110 citations