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.
Highlights
The periodontal pathogen Porphyromonas gingivalis is hypothesized to be important in rheumatoid arthritis (RA) aetiology by inducing production of anti-citrullinated protein antibodies (ACPA)
This study investigated whether raised anti-P. gingivalis antibody levels precede onset of symptoms of RA and the ACPA response in order to elucidate the role of P. gingivalis as a potential trigger of autoimmunity and the development of RA
The anti-Cyclic citrullinated peptide 3 (CPP3) IgG levels were significantly increased in RA patients compared with pre-symptomatic individuals, both when all samples were analysed (4.33 ± 0.59 Arbitrary units (AU)/ml) (Fig. 1b) and when only the sample closest to disease onset was analysed (5.56 ± 0.89 arbitrary units/ml (AU/ml); data not shown); both comparisons were analysed at group level (p < 0.001)
Summary
The periodontal pathogen Porphyromonas gingivalis is hypothesized to be important in rheumatoid arthritis (RA) aetiology by inducing production of anti-citrullinated protein antibodies (ACPA). Rheumatoid arthritis (RA), a complex chronic inflammatory disease with a worldwide prevalence of 0.5–1.0 % [1], is characterized by production of anti-citrullinated protein/peptide antibodies (ACPA) in the majority of patients and persistent inflammation in the synovial tissue of the joints leading to destruction of cartilage and bone [2,3,4]. Elucidation of the potential aetiological link between PD and RA has progressed [8, 10, 11] and a number of studies have identified similarities between these two diseases that possibly explain the epidemiological association Both PD and RA display systemic markers of inflammation (e.g. C-reactive protein and pro-inflammatory cytokines) [6, 12, 13], and an association with HLA-DRB1 alleles [14] and smoking [15, 16] has been described for both RA and PD. An association between PD and established RA could not be confirmed in one of our recent publications [20]
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