Citrullination in the periodontium--a possible link between periodontitis and rheumatoid arthritis.
OBJECTIVE
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.


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.


CONCLUSIONS
In periodontitis, the citrullination of proteins/peptides by human and bacterial peptidylarginine deiminases may generate antibodies after breaching immunotolerance in susceptible individuals.
Department of Periodontology, School of Dental Medicine, University of Bern, Freiburgstrasse 7, CH-3010, Bern, Switzerland.
Oliver
O
Laugisch
Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, 30-387, Krakow, Poland.
Alicia
A
Wong
Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, 30-387, Krakow, Poland.
Aneta
A
Sroka
Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, 30-387, Krakow, Poland.|Malopolska Center of Biotechnology, Jagiellonian University, 30-387, Krakow, Poland.
Tomasz
T
Kantyka
Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, 30-387, Krakow, Poland.
Joanna
J
Koziel
Department of Preventive, Restorative and Pediatric Dentistry, School of Dental Medicine, University of Bern, Bern, Switzerland.
Klaus
K
Neuhaus
Department of Periodontology, School of Dental Medicine, University of Bern, Freiburgstrasse 7, CH-3010, Bern, Switzerland.
Anton
A
Sculean
Kennedy Institute, Nuffield Dept of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7FY, UK.
Patrick J
PJ
Venables
Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, 30-387, Krakow, Poland.|Malopolska Center of Biotechnology, Jagiellonian University, 30-387, Krakow, Poland.|Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY, 40202, USA.
Jan
J
Potempa
Department of Rheumatology, Clinical Immunology and Allergology, University Hospital of Bern, Bern, Switzerland.
Burkhard
B
Möller
Department of Periodontology, School of Dental Medicine, University of Bern, Freiburgstrasse 7, CH-3010, Bern, Switzerland. sigrun.eick@zmk.unibe.ch.
Sigrun
S
Eick
D001172:Arthritis, Rheumatoid / Q000150:complications*; D000076302:Citrullination; D006801:Humans; D010455:Peptides; D010518:Periodontitis / Q000150:complications*; D010519:Periodontium / Q000378:metabolism*; D016966:Porphyromonas gingivalis
D010455:Peptides
Citrullinated peptide antibodies; Citrullination; Periodontitis; Porphyromonas gingivalis; Rheumatoid arthritis