MMP-8 and TIMP-1 are Influenced by Periodontal Inflammation in Patients With Rheumatoid Arthritis Under Methotrexate Immunosuppression

Objectives: This clinical monocentric cohort study aimed to investigate associations between different blood parameters and periodontal condition as well as selected periodontal pathogenic bacteria in patients with rheumatoid arthritis (RA) under immunosuppression with methotrexate (MTX).
Methods: Fifty-six patients (mean age 55.07 ± 11.75 years, female: 27) with RA under MTX immunosuppression were included. Periodontal examination comprised detection of gingival inflammation (PBI), periodontal status with periodontal probing depth (PPD), bleeding on probing (BOP) and clinical attachment loss (CAL). Based on PPD and/or CAL, patients were classified as no/mild periodontitis (no PD) and moderate or severe periodontitis (PD). Furthermore, samples from gingival crevicular fluid (GCF) were collected and analyzed for MMP-8 concentration (ELISA) and the presence of 11 selected periodontal pathogenic bacteria (PCR). Blood samples were analyzed for concentration of different RA-related parameters, including TIMP-1, MMP-8, IFN-γ, TGF-β1, IL-23 and IL-6.
Results: Sixty-one percent of the patients (n=34) were found to have a moderate to severe PD. While prevalence of selected periodontal pathogenic bacteria was higher in PD patients, no substantial influence of bacteria on the investigated blood parameters was found. Both, GCF (no PD: 6.22 ± 7.01, PD: 15.99 ± 13.49; p<0.01) and blood concentration of MMP-8 (no PD: 2.60 ± 3.57, PD: 5.52 ± 5.92; p<0.01) were significantly higher in RA patients with PD; no correlation was found between GCF and blood MMP-8 concentration (Spearman rho: 0.175; p=0.23). Higher BOP values showed significantly higher TIMP-1 and MMP-8 concentration in blood (p<0.01). No influence of BOP values were detected for IFN-γ (p=1.00), TGF-β1 (p=0.94), IL-23 (p=0.10) and IL-6 (p=0.80).
Conclusions: Periodontal inflammation has an influence on MMP-8 and TIMP-1 concentration in blood of RA patients under MTX immunosuppression. The correlation between oral inflammation and changes in MMP-8 and TIMP-1 concentration in blood indicates a preferential activation of innate immune mechanisms.