Background/Purpose: In the disease association between rheumatoid arthrtitis (RA) and periodontitis a potential role is suggested for the periodontal pathogen Porphyromonas gingivalis (PG). PG is a major pathogen in periodontitis and has the unique feature of protein citrullination.  Anti- cyclic-citrullinated-protein (CCP) antibodies are found not only in established RA but are also known to precede RA development. Aim of this study was to assess the levels of anti-PG antibodies in rheumatoid factor (IgM-RF) and/or anti-CCP positive arthralgia patients.

Methods: A cohort of 318 adult IgM-RF and/or anti-CCP positive arthralgia patients (mean age 50 years SD 12, 80% female) was prospectively followed for arthritis development during a median follow-up of 30 months. Patients with the possibility of a false-positive result for IgM-RF were excluded. Baseline analysis of serum samples was done by commercial (anti–CCP2; Axis-Shield) or in-house ELISA (IgM-RF, IgM-, IgG– and IgA– anti-PG). Baseline variables included age, gender, smoking, carriage of shared epitope (SE), and CRP / ESR levels by routine analysis.  Anti-PG titers were compared to control subjects with severe periodontitis (disease controls, n=90) and control subjects with a healthy periodontium (healthy controls, n=23).

Results:  32% (n=103) of the patients developed arthritis, at median 15 months after baseline. After correction for age, gender, smoking and SE carriage, these patients had significantly higher mean anti-CCP levels compared to those who did not develop arthritis (p<0.001). No differences in levels of IgM-RF, anti-PG, CRP and ESR were found between groups of patients who did or did not develop arthritis.

Arthralgia patients had higher mean IgG-anti-PG levels than the healthy controls, as had the disease controls (p<0.001) (table 1). IgA anti-PG levels were only different between disease- and healthy controls (p<0.05), and no differences were seen between arthralgia patients, disease controls, and healthy controls in IgM-anti-PG levels (table 1). However, in the subgroup of arthralgia patients who developed arthritis there was a correlation of IgM-anti-PG with both anti-CCP and IgM-RF levels (ρ=0.2, p<0.05). No correlations were found between IgG- and IgA-anti-PG and anti-CCP.

Conclusion: IgM-RF and/or anti-CCP positive arthralgia patients have elevated IgG-anti-PG titers, and there is a significant correlation of IgM -anti-PG and RA-specific auto-antibodies in arthralgia patients who developed arthritis. This might indicate a role for the periodontal pathogen P. gingivalis in arthritis development.