Citrullination in the periodontium—a possible link between periodontitis and rheumatoid arthritis
      
August 2015
    
              
                Date:
                13 Aug 2015
              
            
Abstract
Objectives
The
 aim of the present study was to assess human and bacterial 
peptidylarginine deiminase (PAD) activity in the gingival crevicular 
fluid (GCF) in the context of serum levels of antibodies against 
citrullinated epitopes in rheumatoid arthritis and periodontitis.
Materials and methods
Human PAD and Porphyromonas gingivalis-derived
 enzyme (PPAD) activities were measured in the GCF of 52 rheumatoid 
arthritis (RA) patients (48 with periodontitis and 4 without) and 44 
non-RA controls (28 with periodontitis and 16 without). Serum antibodies
 against citrullinated epitopes were measured by ELISA. Bacteria being 
associated with periodontitis were determined by nucleic-acid-based 
methods.
Results
Citrullination
 was present in 26 (50 %) RA patients and 23 (48 %) controls. PAD and 
PPAD activities were detected in 36 (69 %) and 30 (58 %) RA patients, 
respectively, and in 30 (68 %) and 21 (50 %) controls, respectively. 
PPAD activity was higher in RA and non-RA patients with periodontitis 
than in those without (p = 0.038; p = 0.004), and was detected in 35 of 59 P. gingivalis-positive samples, and in 16 of 37 P. gingivalis-negative samples in association with high antibody levels against that species.
Conclusions
PAD and PPAD activities within the periodontium are elevated in RA and non-RA patients with periodontitis. PPAD secreted by P. gingivalis
 residing in epithelial cells may exert its citrullinating activity in 
distant regions of the periodontium or even distant tissues.
Clinical relevance
In
 periodontitis, the citrullination of proteins/peptides by human and 
bacterial peptidylarginine deiminases may generate antibodies after 
breaching immunotolerance in susceptible individuals.
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