Salivary citrullinated proteins in rheumatoid arthritis and associated periodontal disease

Sci Rep. 2021 Jun 29;11(1):13525. doi: 10.1038/s41598-021-93008-y.


Periodontal disease (PD) can be an important precipitating factor in the production of citrullinated proteins. Its importance is emphasized, but it is not the only way to produce citrullinated proteins. The aim of the current study was to determine the periodontal conditions and the salivary citrullinated protein content in patients with rheumatoid arthritis (RA) compared to healthy controls. We also wished to correlate citrullinated protein levels in the saliva and serum biomarkers with the periodontal status and temporomandibular joint (TMJ) involvement of patients with RA. Twenty-three patients with RA and 17 healthy controls participated the study. Saliva samples were taken: citrulline content of saliva was measured. Blood test results for patients with RA were collected. TMJ disorders were described. Cariological and periodontal indices were registered. Periodontal conditions and periodontal staging were also registered. Comparison of measured values between groups was performed. Intragroup correlation of patients' values was counted. The prevalence of TMJ complaints was significantly higher in the RA group (8/23) versus controls (1/17). The patients with RA had worse periodontal condition because more patients with RA had gingivitis with a significantly higher bleeding on probing (BOP) (RA: 22.4 ± 25.0%; controls: 6.36 ± 11.6%; p = 0.018). Gingival index (GI) was also significantly higher in the patients than in controls (RA: 0.68 ± 0.58; controls: 0.19 ± 0.38; p = 0.010). The citrullinated protein (relative) content of saliva did not differ significantly (p = 0.147) between patients with RA (1102.2 ± 530.8) and healthy controls (1873.1 ± 1594.9). In RA, the salivary anti-CCP levels positively correlated with PD staging (R = 0.464, p = 0.039) . Control subjects more commonly had healthy gingiva than RA patients. Moreover, in the control group more individuals had intact and reduced height periodontium than periodontitis compared to the RA group. There was no significant difference in the levels of salivary citrulline between patients with RA and controls, despite the significant differences in their periodontal status. Thus, salivary citrulline levels are not associated with RA disease severity.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid* / complications
  • Arthritis, Rheumatoid* / metabolism
  • Biomarkers*
  • Citrullination*
  • Citrulline / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Periodontal Diseases* / etiology
  • Periodontal Diseases* / metabolism
  • Saliva / metabolism*
  • Salivary Proteins and Peptides / metabolism*


  • Biomarkers
  • Salivary Proteins and Peptides
  • Citrulline