Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Moderate to Severe Adult Periodontitis Increases Risk of Rheumatoid Arthritis in Non-Smokers and Is Associated with Elevated ACPA Titers: The ARIC Study

Molitor1,  J. A., Alonso1,  A., Wener2,  M.H., Michalowicz3,  B.S., Beck4,  J., Gersuk5,  V. H., Buckner5,  J.H.

Univ of MN, Minneapolis, MN,
Univ of WA, Seattle, WA,
Univ of MN, Minneapolis,
Univ of NC, Chapel Hill,
Benaroya Rsch Ini., Seattle, WA

Purpose:

Genetic risks for the development of anti-citrullinated peptide antibodies (ACPA) have been established, but the only environmental exposure consistently associated with ACPA+ Rheumatoid Arthritis (RA) risk is tobacco exposure (TE).

Objectives:

1. Establish the risk for development of incident (new) RA cases in a large cohort characterized for periodontitis severity and smoking status. 2. Assess ACPA and RF seropositivity of RA cases.

Method:

We studied 6616 participants in the Atherosclerosis Risk in Communities (ARIC) study who were examined 4 times during the period 1987–1998 and for whom a detailed periodontal assessment was made in 1996–1998. Periodontitis status (no, mild, moderate or severe disease) was determined using published criteria. Subjects hospitalized with a discharge code of RA in the 9 years before their periodontal exam were designated as having "prevalent" RA; those with a first-time RA discharge code up to 8 years following their periodontal assessment were designated as having "incident" RA. Hazard ratios (HR) were determined using the Cox proportional hazards model adjusting for age, sex, and race. Available sera from 1990–92 and 1996–98 from both the incident and prevalent RA cases were examined with a second-generation ACPA ELISA and ELISA for IgG-RF, IgA-RF, and IgM-RF. HLA- DR4 alleles were determined by quantitative real-time PCR.

Results:

Incidence rates of RA in the ARIC cohort were comparable to those in Olmsted County, MN. The HR of developing RA in subjects with moderate to severe periodontitis (n= 27) was 2.6 (95% CI=1.0–6.4, p=0.04), compared to those with no to mild periodontitis (n= 6). Among lifetime non-smokers, the HR was 8.8 (95% CI=1.1–68.9, p=0.04). In adjusted analyses, periodontitis severity was not associated with RA incidence among current and former smokers. ACPA levels were significantly higher in participants with moderate-severe periodontitis than in those with no-mild periodontitis (222.5 U vs. 8.4 U, p=0.04). Of 13 cases with ACPA+ at either sampled visit, 11 were both smokers and had moderate-severe periodontitis (85%, vs 47% predicted, chi-square, P=0.007), indicating a possible interaction between smoking and periodontitis in the production of ACPA. Of 12 DR4+ participants, 6/7 ACPA+ were both smokers and had moderate-severe periodontitis, whereas only 1/5 ACPA-/DR4+ individuals was both a smoker and had moderate-severe periodontitis (p=0.07, Fisher's exact test).

Conclusion:

Moderate to severe periodontitis may be a risk factor for the development of RA in non-smokers. Individuals with moderate to severe periodontitis have higher ACPA titers than those with no or mild periodontitis. There is evidence of an interaction between smoking and periodontitis increasing the likelihood of high-titer ACPA.

Supported by the Minnesota Medical Foundation and RO1DE11551.

To cite this abstract, please use the following information:
Molitor, J. A., Alonso, A., Wener, M.H., Michalowicz, B.S., Beck, J., Gersuk, V. H., et al; Moderate to Severe Adult Periodontitis Increases Risk of Rheumatoid Arthritis in Non-Smokers and Is Associated with Elevated ACPA Titers: The ARIC Study [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1160
DOI: 10.1002/art.26234

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