Background/Purpose: Periodontitis and immune responses to periodontal pathogens such as Porphyromonas gingivalis (Pg) are associated with rheumatoid arthritis (RA) but the mechanisms underlying these connections are incompletely understood. Our goal here was to gain further insights into inflammatory responses linking periodontal and joint inflammation in RA patients.

Methods: Seventy-three subjects underwent full-mouth dental examinations, including 33 RA patients, the majority with early RA (median symptom duration 5.5 months), all meeting 2010 ACR/EULAR criteria, 20 age and gender matched healthy subjects (HS), and 20 chronic periodontitis subjects who lacked RA (non-RA CP). Thirteen inflammatory mediators and matrix metalloproteinases (MMPs) were measured in serum, saliva, gingival crevicular fluid (GCF) and synovial fluid by bead-based multiplex immunoassay. Pg DNA in subgingival plaque Pg IgG antibodies in serum and were also measured.

Results: Of the 33 RA patients, 30 (91%) received routine dental care, and only one currently smoked. However, on clinical assessment, only 10 of the 33 patients (30%) had healthy periodontium, 13 (39%) had gingivitis, a periodontitis precursor, and 10 (30%) had periodontitis.

Compared with HS and non-RA CP, RA patients had the most elevated serum levels of inflammatory mediators and MMPs, with exception of MMP-3, which was more enriched in the sera of non-RA CP patients (P< 0.005 vs. HS). In RA synovial fluid, the Th1-associated mediator, CXCL10, innate immune mediators, IL-6 and IL-8, and MMPs, particularly MMP-1 and MMP-3, were most concentrated compared with serum (P≤0.0001).

In saliva, the non-RA CP group had greatest concentration of inflammatory mediators, particularly the neutrophil chemoattractant IL-8, and elevated levels of MMPs, especially MMP-1, MMP-8, and MMP-9 (P< 0.002). In GCF, a similar inflammatory profile was observed and additionally levels of the anti-inflammatory cytokine IL-10 were significantly lower than in HS. Although values were somewhat lower, RA patients also had elevation of IL-8 in both saliva and GCF (P=0.02), and levels of MMP-8, and MMP-9 were also elevated, particularly in saliva (P< 0.002). Similar to the non-RA chronic periodontitis group, levels of IL-10 were decreased in GCF of RA patients compared with HS (P=0.005). When RA patients were stratified according to dental status (healthy, gingivitis, or periodontitis), there were no significant differences in the levels of inflammatory mediators. In contrast, Pg antibodies in serum or Pg DNA in subgingival plaque were found only in RA patients with clinical periodontitis.

Conclusion: While RA patients had systemic and joint inflammation, as expected, they also had elevated levels of periodontitis-associated mediators in oral fluids, even in the absence of clinical periodontitis. Levels of IL-8, a chemoattractant for neutrophils, the major effector cell in periodontitis, and MMPs were particularly elevated. Thus, the oral mucosa may be a common, but often unrecognized, site of extra-articular inflammation in RA. In contrast, Pg antibodies and DNA seem to be a marker only for frank periodontitis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/subclinical-oral-inflammation-is-common-across-the-spectrum-of-oral-findings-in-rheumatoid-arthritis-patients-whereas-porphyromonas-gingivalis-antibodies-are-primarily-a-marker-for-clinical-periodont/