Background Both Peptydil arginine deiminase of P. gingivalis (pPAD), and the human enzyme (hPAD), could citrullinarize peptides from the bacteria and human host in Rheumatoid Arthritis patients (RA). Chronic periodontitis (CP) could be associated with a constant generation of citrullinated proteins, and it lead to a proportional hPAD enzymatic production.

Objectives The aim was to demonstrate the association between serum levels of hPAD4 and severe Periodontitis in patients with rheumatoid arthritis.

Methods Patients with RA (n=127) matched with healthy controls (n=120) were studied in a cross-sectional study. Levels of human recombinant antigens for hPAD4; cyclic citrullinated peptide antibody (CCP3, IgG), Rheumatoid factor (IgM) and C-reactive protein (CRP); determined by ELISA test.

The CP was classified according to the recommendations of the International Workshop for Classification of Periodontal Diseases and Conditions. Bivariate analysis to demonstrate the associations, and non-parametric analyzes were used according to the case.

Results There were no significant demographic diffrences between the two groups. The median hPAD4 level was 1.21 (95% CI 1.4–1.7) in RA and 0.75 (95% CI 0.94–1.26) ng/ml in controls, (p<0.004). The median hPAD4 level in patients with RA and CP was 1.32 (95% CI 1.39–1.9) Vs control with CP 0.7 (95% CI 0.94–1.5) ng/ml, p<0.04.

The frequency of CP was higher in patients with RA than in controls (66.9 vs 43%, p<0.000; OR: 2.65 (95% CI: 1.58–4.44); these values showed a low correlation (0.24). The median level of hPAD4 was associated with CP extension, p<0.000 and severity, p<0.000.

A significant correlation was found between levels of hPAD4 with the DAS28 ESR score (p<0.002). The high score of HAQ-DI (>2.0) correlated with hPAD4 levels (P<0.001). The group of people with higher HAQ-DI score and at the same time with greater severity of CP (n=12) showed increased levels PAD4 (p<0.025).

Conclusions hPAD4 levels correlate with the severity of CP independent of the RA presence and in RA subjects with high score of disability and activity disease. The hPAD4 could be proposed as a serological marker of clinical severity in chronic diseases such as CP and RA.

References

1. Rose, H.M., C. Ragan, and et al., Differential agglutination of normal and sensitized sheep erythrocytes by sera of patients with rheumatoid arthritis. Proc Soc Exp Biol Med, 1948. 68(1): p. 1–6.

2. Girbal-Neuhauser, E., et al., The epitopes targeted by the rheumatoid arthritis-associated antifilaggrin autoantibodies are posttranslationally generated on various sites of (pro)filaggrin by deimination of arginine residues. J Immunol, 1999. 162(1): p. 585–94.

3. Lundberg, K., et al., Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase. Arthritis Rheum, 2008. 58(10): p. 3009–19.

4. Mikuls, T.R., et al., Periodontitis and Porphyromonas gingivalis in patients with rheumatoid arthritis. Arthritis Rheumatol, 2014. 66(5): p. 1090–100.

References

Disclosure of Interest None declared