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

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ABSTRACT

Background: The 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.

Methods: A 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.

Results: Anti-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.

Conclusions: Anti-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 material: The online version of this article (doi:10.1186/s13075-016-1100-4) contains supplementary material, which is available to authorized users.

No MeSH data available.


Concentrations of anti-RgpB (a) and anti-CPP3 (b) antibodies in controls, pre-symptomatic individuals and patients with RA. Mean concentrations marked as a grey line. ***p < 0.001. n.s not significant
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Fig1: Concentrations of anti-RgpB (a) and anti-CPP3 (b) antibodies in controls, pre-symptomatic individuals and patients with RA. Mean concentrations marked as a grey line. ***p < 0.001. n.s not significant

Mentions: The concentration of anti-RgpB IgG was significantly increased in RA patients (mean ± SEM 114.4 ± 16.9 AU/ml) and in particular in pre-symptomatic individuals, calculated using all 422 samples (152.7 ± 14.8 AU/ml) or one sample per individual (when more than one sample was available, the sample closest to symptom onset was chosen) (133.4 ± 16.2 AU/ml; data not shown), compared with control subjects (82.2 ± 12.1 AU/ml, p < 0.001 for all three groups) (Fig. 1a).Fig. 1


Concentration of antibodies against Porphyromonas gingivalis is increased before the onset of symptoms of rheumatoid arthritis
Concentrations of anti-RgpB (a) and anti-CPP3 (b) antibodies in controls, pre-symptomatic individuals and patients with RA. Mean concentrations marked as a grey line. ***p < 0.001. n.s not significant
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5015325&req=5

Fig1: Concentrations of anti-RgpB (a) and anti-CPP3 (b) antibodies in controls, pre-symptomatic individuals and patients with RA. Mean concentrations marked as a grey line. ***p < 0.001. n.s not significant
Mentions: The concentration of anti-RgpB IgG was significantly increased in RA patients (mean ± SEM 114.4 ± 16.9 AU/ml) and in particular in pre-symptomatic individuals, calculated using all 422 samples (152.7 ± 14.8 AU/ml) or one sample per individual (when more than one sample was available, the sample closest to symptom onset was chosen) (133.4 ± 16.2 AU/ml; data not shown), compared with control subjects (82.2 ± 12.1 AU/ml, p < 0.001 for all three groups) (Fig. 1a).Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

Background: The 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.

Methods: A case&ndash;control study (251 cases, 198 controls) was performed within the Biobank of Northern Sweden. Cases had donated blood samples (n&thinsp;=&thinsp;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.

Results: Anti-RgpB IgG levels were significantly increased in pre-symptomatic individuals (mean&thinsp;&plusmn;&thinsp;SEM; 152.7&thinsp;&plusmn;&thinsp;14.8&nbsp;AU/ml) and in RA patients (114.4&thinsp;&plusmn;&thinsp;16.9&nbsp;AU/ml), compared with controls (p&thinsp;&lt;&thinsp;0.001). Anti-CPP3 antibodies were detected in 5&nbsp;% of pre-symptomatic individuals and in 8&nbsp;% of RA patients, with elevated levels in both subsets (4.33&thinsp;&plusmn;&thinsp;0.59 and 9.29&thinsp;&plusmn;&thinsp;1.81&nbsp;AU/ml, respectively) compared with controls (p&thinsp;&lt;&thinsp;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.

Conclusions: Anti-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 material: The online version of this article (doi:10.1186/s13075-016-1100-4) contains supplementary material, which is available to authorized users.

No MeSH data available.