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Citrullination in the periodontium—a possible link between periodontitis and rheumatoid arthritis



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.


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.


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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The authors would like to thank Marianne Weibel (Department of Periodontology, Laboratory of Oral Microbiology, School of Dental Medicine, University of Bern) for technical assistance. We are indebted to Walter Bürgin (University of Bern) for statistical advice.


The study was funded by the participating departments and a research grant of the German Society of Periodontology (DGParo/GABA), along with grants from US NIH (DE 022597), the European Commission (FP7-PEOPLE-2011-ITN-290246 “RAPID” and FP7-HEALTH-F3-2012-306029 “TRIGGER”), Polish National Centre of Science project OPUS 2012/05/B/NZ6/00581, and Polish Ministry of Science and Higher Education (project 2975/7.PR/13/2014/2). Faculty of Biochemistry, Biophysics and Biotechnology of Jagiellonian University is a partner of the Leading National Research Center (KNOW) supported by the Ministry of Science and Higher Education. Oliver Laugisch was supported by German Academic Exchange Service (grant No: 314-D/08/48763) and the German Society of Periodontology (grant for a foreign training and research grant).

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The authors declare that they have no competing interests.

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Correspondence to Sigrun Eick.

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Laugisch, O., Wong, A., Sroka, A. et al. Citrullination in the periodontium—a possible link between periodontitis and rheumatoid arthritis. Clin Oral Invest 20, 675–683 (2016).

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  • Periodontitis
  • Rheumatoid arthritis
  • Citrullination
  • Porphyromonas gingivalis
  • Citrullinated peptide antibodies