Background/Purpose:  Periodontitis shares pathogenic mechanisms with rheumatoid arthritis (RA) and may trigger its onset. However, little information is available about inflammatory responses in oral fluids of RA patients.

Methods:   33 RA patients (22 new-onset, 11 late RA), all meeting 2010 ACR/EULAR criteria, 20 age/gender-matched healthy subjects (HS) without periodontitis/RA, and 20 patients with chronic periodontitis (CP) without RA were enrolled. 20 analytes including matrix metalloproteinases (MMPs) and innate/adaptive immune mediators were measured by Luminex in serum, saliva, gingival crevicular fluid (GCF), and RA joint fluid (JF). Serum P. gingivalis (Pg) IgG was measured.

Results:   The 33 patients were typical of RA cohorts (85% female, median age 51) and only one currently smoked. The majority (91%) received regular dental care with cleanings every 6 months. 58% had rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA). Of the RA patients, 10 (30%) had periodontal health, 13 (39%) had gingivitis, and 10 (30%) had periodontitis. Pocket depth (PD), clinical attachment loss (CAL), and bleeding on probing (BOP) were all increased compared with HS (P<0.002). Six of 33 patients had Pg IgG antibodies, and all 6 had periodontitis (P=0.0002). Pg antibodies strongly correlated with PD, BOP, and CAL (P≤0.0009). ACPA and RF levels also correlated with CAL (P=0.03). Most mediators were significantly elevated in serum of RA patients versus HS; Th-1 mediators predominated in JF. However, RA patients had elevated salivary levels of IL-17, IL-10, IL-8, OPG, MMP-1, MMP-9, and MMP-13 versus HS (P≤0.03). In GCF IL-8, MMP-8, and MMP-9 amounts were higher in RA versus HS (P≤0.02). Notably in RA patients, MMP-8 or MMP-9 levels were even higher in the oral fluids than serum (P<0.0001) and JF. Salivary or GCF mediators were elevated in RA patients regardless of periodontitis. While 13 patients had elevation of MMP-8 or MMP-9 in saliva >3 SD above the mean of HC, only 30% had clinical periodontitis. In patients with non-RA CP, levels of MMPs were exceptionally elevated in serum and oral fluids compared to HS and RA, particularly MMP-8 and MMP-9 (P<0.0001). Highest levels were seen in GCF, which were 4X higher than serum. The subset of RA patients with CP had similar inflammatory profiles to CP without RA, with exception of a few inflammatory mediators enriched in RA, notably IL-12p70 in saliva (P=0.001), IFNα and CXCL10 in GCF (P≤0.003). MMP levels were higher in all sites for non-RA CP (P≤0.01). Pg antibodies did not directly correlate with any serum mediator, however in GCF, the most proximal site of periodontitis, they correlated with levels of IFNα, IL-10, IL-12p70, and IL-23 (P≤0.05).

Conclusion:  RA patients had oral inflammation despite lack of smoking and regular dental care. Highly elevated MMP levels and correlation between dental parameters and ACPA support pathogenic connections between the diseases.  Pg antibodies may be a marker of periodontitis in RA patients. However, elevation of MMPs in oral sites, regardless of periodontitis status or Pg antibodies, suggests the oral muscosa may be a common, and often unrecognized, site of extra-articular inflammation in RA patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/elevated-matrix-metalloproteinases-levels-in-oral-fluids-of-most-rheumatoid-arthritis-patients-even-without-frank-periodontitis/