Concentration of antibodies against Porphyromonas gingivalis is increased before the onset of symptoms of rheumatoid arthritis

Abstract

BackgroundThe periodontal pathogen Porphyromonas gingivalis is hypothesized to be important in rheumatoid arthritis (RA) aetiology by inducing production of anti-citrullinated protein antibodies (ACPA). We have shown that ACPA precede RA onset by years, and that anti-P. gingivalis antibody levels are elevated in RA patients. The aim of this study was to investigate whether anti-P. gingivalis antibodies pre-date symptom onset and ACPA production.MethodsA case–control study (251 cases, 198 controls) was performed within the Biobank of Northern Sweden. Cases had donated blood samples (n = 422) before the onset of RA symptoms by 5.2 (6.2) years (median (interquartile range)). Blood was also collected from 192 RA patients following diagnosis. Antibodies against P. gingivalis virulence factor arginine gingipainB (RgpB), and a citrullinated peptide (CPP3) derived from the P. gingivalis peptidylarginine deiminase enzyme, were analysed by ELISA.ResultsAnti-RgpB IgG levels were significantly increased in pre-symptomatic individuals (mean ± SEM; 152.7 ± 14.8 AU/ml) and in RA patients (114.4 ± 16.9 AU/ml), compared with controls (p < 0.001). Anti-CPP3 antibodies were detected in 5 % of pre-symptomatic individuals and in 8 % of RA patients, with elevated levels in both subsets (4.33 ± 0.59 and 9.29 ± 1.81 AU/ml, respectively) compared with controls (p < 0.001). Anti-CPP3 antibodies followed the ACPA response, with increasing concentrations over time, whilst anti-RgpB antibodies were elevated and stable in the pre-symptomatic individuals with a trend towards lower levels after RA diagnosis.ConclusionsAnti-P. gingivalis antibody concentrations were significantly increased in RA patients compared with controls, and were detectable years before onset of symptoms of RA, supporting an aetiological role for P. gingivalis in the development of RA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1100-4) contains supplementary material, which is available to authorized users.

Association of Distinct Fine Specificities of Anti−Citrullinated Peptide Antibodies With Elevated Immune Responses to Prevotella intermedia in a Subgroup of Patients With Rheumatoid Arthritis and Periodontitis

“…However, we observed no association between any ACPA and these antibodies. In contrast to previous studies in 2 well‐documented Swedish cohorts, we observed no association of anti‐RgpB with CCP‐2–positive RA, nor did we observe elevated anti‐RgpB levels in RA patients compared to OA patients, or in CCP‐2–positive RA patients compared to CCP‐2–negative RA patients . Our data are consistent with previous studies showing no association of anti‐RgpB antibodies with RA or pre‐RA and no difference in anti– P gingivalis outer membrane antibody levels between RA and non‐RA cohorts .…”

“…Anti‐RgpB antibody levels, used as an additional marker for P gingivalis infection as in previous publications , correlated well with anti− P gingivalis antibody levels and were significantly higher in RA patients with PD than in RA patients without PD. However, we observed no association between any ACPA and these antibodies.…”

Individuals at risk of seropositive rheumatoid arthritis: the evolving story

“…Instead, experimental evidence has demonstrated that this pathogen can promote autoimmune arthritis in mice through stimulation of toll-like receptor (TLR)-2 and IL-1driven Th17 response [103]. In humans, antibodies to gingipain B, a major virulence factor of P. gingivalis, are detected in samples collected before onset of symptoms of RA, supporting exposure to P. gingivalis during preclinical period [104]. However, although the presence of periodontitis was associated with progression to RA in a cohort of patients with arthralgia, this process was not linked to the presence of P. gingivalis in subgingival biofilm [105].…”

Erratum to: Concentration of antibodies against Porphyromonas gingivalisis increased before the onset of symptoms of rheumatoid arthritis

“…Unfortunately, after publication of this article [1], it was noticed that the x-axis markers for Fig. 2a and b were incorrect.…”