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Background  A relationship between rheumatoid arthritis (RA) and periodontitis has been suggested from findings that individuals with RA are prone to have advanced periodontitis and vice versa. In search of possible common pathogenetic features of these two diseases, we investigated the presence of citrullinated proteins and expression of endogenous peptidylarginine deiminases  ( PAD2 and PAD4), in periodontal tissue of individuals with periodontitis and healthy controls, in relation to the periodontal pathogens  Porphyromonas gingivalis  ( P. gingivalis ) and  Aggregatibacter actinomycetemcomitans  ( A. actinomycetemcomitans ), producing leukotoxin as virulence factor. These two oral bacteria have been suggested to be linked to anti-citrullinated protein antibodies in patients with RA.    Methods  Gingival tissue biopsies were obtained from 15 patients with periodontitis and 15 individuals without periodontal disease. Presence of CD3-positive lymphocytes, citrullinated proteins, PAD2, PAD4,  P. gingivalis  as well as  A. actinomycetemcomitans  and  Mannheimia haemolytica  produced leukotoxins were analysed by immunohistochemistry, followed by triple-blind semi-quantitative analysis. Mann–Whitney and Fisher’s exact tests were used to analyse differences between groups.  PADI2  and  PADI4  mRNA levels were assessed by RT-qPCR and analysed using Wilcoxon signed rank test.    Results  Increased staining of citrullinated proteins was observed in gingival connective tissue from subjects with periodontitis (80%, 12/15) compared to healthy gingival tissue (27%, 4/15), whereas no differences were observed in gingival epithelium. There was also an increased staining of the citrullinating enzymes PAD2 and PAD4 in gingival connective tissue of patients with periodontitis whereas similar levels of PAD2 and PAD4 were observed in the gingival epithelium of the two groups. Similarly, the mRNA levels of  PADI2  and  PADI4  were also increased in the gingival tissue of patients with periodontitis compared to healthy controls. Furthermore, presence of  P. gingivalis  and leukotoxins was comparable in both epithelium and connective tissue, from the different investigated individuals with and without periodontitis, and there were no correlations between the presence of periodontal pathogens and the expression of citrullinated proteins or PAD enzymes.    Conclusion  Chronic gingival inflammation is associated with increased local citrullination and PAD2 and PAD4 expression in periodontitis. The increased citrullination and PAD2 and PAD4 expression in periodontitis were, however, independent of the presence of periodontal pathogen  P. gingivalis  and  A. actinomycetemcomitans  leukotoxin.    Electronic supplementary material  The online version of this article (10.1186/s12967-018-1588-2) contains supplementary material, which is available to authorized users.

journal of translational medicine

Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitis