Background Although the expression of bacterial Peptidyl-Arginine Deiminase (PAD) derived from P. gingivalis seems critical in explaining the potential effects of severe periodontitis in the development of Rheumatoid arthritis (RA), the association with the presence of the bacteria or anti-P. gingivalis/anti-PPAD antibodies is not always evident suggesting that other bacteria could be involved in the link between oral microbiota and citrullination of host proteins.
Objectives To confirm the association between RA disease activity in a homogeneous population (aCCP+ RA patients), oral PAD activity and the prevalence of other bacterial strains such as T. forsythia.
Methods RA patients fulfilling ACR/EULAR 2010 criteria were evaluated from a periodontal (Periodontal Screening Recoding Index) and rheumatologic standpoint. Patients with Sjögren's syndrome or sicca symptons were excluded. Disease activity was measured using DAS28 (ESR). Oral PAD activity was measured by colorimetric assay and presence of Porphyromonas gingivalis, Tannerella forsythia and Prevotella intermedia was evaluated by PCR. Autoantibody levels were determined by ELISA. Multivariate analysis adjusted for gender, age, time since onset of disease, RF and ESR. Comparisons between groups were performed by Mann-Whitney U testing or Kruskal–Wallis testing per the t variables. Spearman correlation testing was employed to correlate PAD activity and DAS28. Statistical significance was set at 0.05%.
Results 132 patients were included. After a multivariate analysis an association was observed between severe periodontitis/dental mobility with moderate/high RA disease activity (OR: 4.4 (1.8–14.0), p=0.04 and 3.4 (1.1–13.4), p=0.03, respectively). Additionally, presence of P. gingivalis and T. forsythia, but not P. intermedia, was significantly associated with moderate/high RA disease activity (3.4 (1.1–10.5), p<0.05 and 4.4 (1.2–10.9), p<0.05). Comparing PAD activity in saliva samples of RA patients we found significant differences between the low (2.3±0.5), moderate (3.4±0.8) and high (4.3±0.3) disease activity subgroups (p<0.01%), whereas patients in remission demonstrated a PAD activity similar to the low disease activity group (1.9±0.39). Additionally, we found a significant correlation between oral PAD activity and RA activity, but not with autoantibody titers.
Conclusions These results show that RA activity is associated with severe periodontitis, high oral PAD activity and the presence of T. forsythia and P. gingivalis, suggesting that both bacteria equally participate in PAD activity present in the oral microenvironment.
Acknowledgements Disclosure: This work was supported by a grant from SEP/CONACYT CB-2010 (#155392).
Disclosure of Interest None declared