Clinical correlations with Porphyromonas gingivalis antibody responses in patients with early rheumatoid arthritis

Abstract

Introduction: Prior studies have demonstrated an increased frequency of antibodies to Porphyromonas gingivalis (Pg), a leading agent of periodontal disease, in rheumatoid arthritis (RA) patients. However, these patients generally had long-standing disease, and clinical associations with these antibodies were inconsistent. Our goal was to examine Pg antibody responses and their clinical associations in patients with early RA prior to and after disease-modifying antirheumatic drug (DMARD) therapy.

Methods: Serum samples from 50 DMARD-naïve RA patients were tested using an enzyme-linked immunosorbent assay with whole-Pg sonicate. For comparison, serum samples were tested from patients with late RA, patients with other connective tissue diseases (CTDs), age-similar healthy hospital personnel and blood bank donors. Pg antibody responses in early RA patients were correlated with standard RA biomarkers, measures of disease activity and function.

Results: At the time of enrollment, 17 (34%) of the 50 patients with early RA had positive immunoglobulin G (IgG) antibody responses to Pg, as did 13 (30%) of the 43 patients with late RA. RA patients had significantly higher Pg antibody responses than healthy hospital personnel and blood bank donors (P < 0.0001). Additionally, RA patients tended to have higher Pg antibody reactivity than patients with other CTDs (P = 0.1), and CTD patients tended to have higher Pg responses than healthy participants (P = 0.07). Compared with Pg antibody-negative patients, early RA patients with positive Pg responses more often had anti-cyclic citrullinated peptide (anti-CCP) antibody reactivity, their anti-CCP levels were significantly higher (P = 0.03) and the levels of anti-Pg antibodies correlated directly with anti-CCP levels (P < 0.01). Furthermore, at the time of study entry, the Pg-positive antibody group had greater rheumatoid factor values (P = 0.04) and higher inflammatory markers (erythrocyte sedimentation rate, or ESR) (P = 0.05), and they tended to have higher disease activity scores (Disease Activity Score based on 28-joint count (DAS28)-ESR and Clinical Disease Activity Index) and more functional impairment (Health Assessment Questionnaire). In Pg-positive patients, greater disease activity was still apparent after 12 months of DMARD therapy.

Conclusions: A subset of early RA patients had positive Pg antibody responses. The responses correlated with anti-CCP antibody reactivity and to a lesser degree with ESR values. There was a trend toward greater disease activity in Pg-positive patients, and this trend remained after 12 months of DMARD therapy. These findings are consistent with a role for Pg in disease pathogenesis in a subset of RA patients.

Figure 1

Porphyromonas gingivalis immunoglobulin G antibody responses. Porphyromonas gingivalis (Pg) antibody responses are shown in age-similar healthy hospital personnel and blood bank donors, in patients with early or late RA and in patients with other connective tissue diseases (CTDs), including 17 patients with lupus and another group consisting of 10 patients with Sjögren syndrome, 4 with scleroderma and 3 with mixed CTD. (A) All data points are shown for each individual group. (B) The results are summarized, and data from all healthy control participants and patients with CTD or RA are combined. In (B), the histograms give the mean values, and I-bars show the standard error of the mean. The shaded region represents <2 SD above the mean absorbance of healthy hospital personnel. Abs: absorbance; IgG: immunoglobulin G.

Figure 2

Anti-cyclic citrullinated peptide antibody levels in rheumatoid arthritis patients and comparison groups. Anti-cyclic citrullinated peptide (anti-CCP) antibody responses are shown in age-similar healthy hospital personnel, patients with connective tissue diseases and early and late rheumatoid arthritis patient groups. Mean values and standard errors of the mean are shown, and the shaded region represents negative values.

Figure 3

Correlation of Porphyromonas gingivalis antibody levels and standard rheumatoid arthritis biomarkers. In the patients with early rheumatoid arthritis (RA), the levels of autoantibodies (anti-cyclic citrullinated peptide (anti-CCP) (A) and rheumatoid factor (RF)) and inflammatory markers (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) (B) were compared at study entry in the 17 patients with positive Porphyromonas gingivalis (Pg) antibody responses and in the 33 patients with negative Pg antibody reactivity, as shown in the left panels. In the right panels, the levels of each RA biomarker are correlated with Pg immunoglobulin G antibody levels (Pearson correlation coefficients). Median values and interquartile ranges are shown, and the shaded regions represent normal values. Ab: antibody; OD: optical density.

Figure 4

Disease activity prior to and after 12 months of disease-modifying antirheumatic drug treatment. Disease activity scores and functional measures ( Disease Activity Score based on 28-joint count erythrocyte sedimentation rate (DAS28-ESR), ESR, Clinical Disease Activity Index (CDAI), and Health Assessment Questionnaire (HAQ)) are shown according to Porphyromonas gingivalis (Pg) antibody status at the time of study entry, prior to disease-modifying antirheumatic drug therapy and after 12 months of treatment. Data were available at the time of study entry for all 17 Pg-positive and all 33 Pg-negative patients. At the 12-month follow-up visits, data for DAS28-ESR, ESR and CDAI were available from 16 Pg-positive and 22 Pg-negative patients. For the HAQ, data were available from 12 Pg-positive and 22 Pg-negative patients. Median values and interquartile ranges are shown, and the shaded regions represent normal or negative values. Although disease activity measures declined in both groups during the 12-month period, patients with Pg antibodies tended to have higher values, primarily for ESR and DAS28-ESR.