The P. gingivalis Autocitrullinome Is Not a Target for ACPA in Early Rheumatoid Arthritis

Area of Science:

• Microbiology
• Immunology
• Rheumatology

Background:

• Rheumatoid arthritis (RA) is linked to periodontal disease, driven by Porphyromonas gingivalis.
• P. gingivalis produces peptidylarginine deiminase (PPAD), capable of protein citrullination.
• Previous research showed P. gingivalis disrupts gut barrier and worsens joint inflammation.

Purpose of the Study:

• To investigate if P. gingivalis PPAD activity contributes to rheumatoid arthritis (RA) pathogenesis by generating anticitrullinated protein antibodies (ACPA).
• To assess if autocitrullinated P. gingivalis proteins trigger ACPA production in early arthritis patients.
• To determine PPAD's role in P. gingivalis-induced gut barrier dysfunction and arthritis exacerbation.

Main Methods:

• Utilized a P. gingivalis W50 PPAD mutant strain lacking citrullination activity.
• Analyzed serum from disease-modifying antirheumatic drug-naïve early arthritis patients.
• Evaluated P. gingivalis-mediated intestinal barrier breakdown and joint inflammation in a murine model.

Main Results:

• No evidence of patient antibodies targeting autocitrullinated P. gingivalis proteins was found.
• PPAD deletion did not prevent P. gingivalis-induced intestinal barrier breakdown.
• PPAD deletion did not prevent P. gingivalis-induced exacerbation of inflammatory arthritis in mice.

Conclusions:

• The enzymatic activity of P. gingivalis PPAD is not a significant factor in initiating ACPA production.
• PPAD's citrullination activity is not a major virulence mechanism in early-stage inflammatory arthritis.
• P. gingivalis may contribute to RA through mechanisms independent of PPAD's enzymatic function.