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



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.



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.



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.
Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden.
Linda
L
Johansson
Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Natalia
N
Sherina
Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Nastya
N
Kharlamova
Department of Oral Immunology and Infectious Diseases, University of Louisville, School of Dentistry, Louisville, KY, USA.
Barbara
B
Potempa
Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Barbro
B
Larsson
Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Lena
L
Israelsson
Department of Oral Immunology and Infectious Diseases, University of Louisville, School of Dentistry, Louisville, KY, USA.|Department of Microbiology, and Malopolska Centre of Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
Jan
J
Potempa
Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden. solbritt.rantapaa.dahlqvist@umu.se.
Solbritt
S
Rantapää-Dahlqvist
Rheumatology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Karin
K
Lundberg
D018829:Adhesins, Bacterial / Q000276:immunology; D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D016866:Bacteroidaceae Infections / Q000276:immunology*; D016022:Case-Control Studies; D003546:Cysteine Endopeptidases / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000080867:Gingipain Cysteine Endopeptidases; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010456:Peptides, Cyclic / Q000276:immunology; D016966:Porphyromonas gingivalis / Q000276:immunology
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D003546:Cysteine Endopeptidases
Anti-citrullinated protein/peptide antibodies; Antibodies; Arginine gingipainB; Citrullinated peptide; Porphyromonas gingivalis; Predating onset; Rheumatoid arthritis