Periodontal Pathogen Antibodies Precede RA Symptom Onset

Antibodies against antigens from the periodontal pathogen Porphyromonas gingivalis are increased in patients with rheumatoid arthritis (RA) compared with controls. These antibodies are measurable in the serum of patients years prior to the first onset of arthritic symptoms, suggesting an etiologic link between the development of RA and P gingivalis.

In a case-control study published in Arthritis Research & Therapy, researchers at Umeå University, Sweden, analyzed blood samples from 2 ongoing, population-level health survey cohorts in Sweden: the Medical Biobank and the Maternity cohort. Patients who fulfilled the American Rheumatism Association 1987 revised criteria for RA were then cross-referenced with medical record data from the 2 survey cohorts, resulting in 251 cases analyzed.

Blinded analyses of antibody titers against the virulence factor arginine gingipain type B (RgpB) protein purified from P gingivalis, synthetic cyclic citrullinated peptide (CPP3), and the arginine-containing control peptide (RPP3) were then measured by enzyme-linked immunosorbent assay (ELISA). 

Receiver operating characteristic curves were used to designate cut-off values defining anti-CCP3 immunoglobulin G (IgG) positivity, which were set at >29.19 AU/mL, resulting in a specificity of 96%. Absence of clinical data with regard to history of chronic periodontitis (PD) resulted in the inability to define a set cut-off value for anti-RgpB IgG response positivity.

Patients with RA had significantly increased concentrations of anti-RgpB IgG (mean ± SEM 114.4 ± 16.9 AU/mL) compared with controls (82.2 ± 12.1 AU/mL, P <.001). This relationship remained significant when analyzing individuals who were still presymptomatic (P <.001).

Patients with RA also had significantly increased concentrations of anti-CCP3 IgG (mean ± SEM 9.29 ± 1.81 AU/mL) compared with patients who were presymptomatic (4.33 ± 0.59 AU/mL, P <.001) and when compared with controls (2.36 ± 0.58 AU/mL, P <.001).

These anti-CCP3 IgG antibodies were found in 5% of individuals who were later diagnosed with RA but did not currently display any symptoms and in 8% of those with symptomatic RA.  Anti-CCP3 IgG also appeared to correlate with anti-citrullinated protein/peptide antibody (ACPA) response.

Moreover, anti-CCP3 IgG accumulated frequency increased over time, positively correlating over time to first RA symptom onset. This trend appeared to “mimic that of the ‘classical’ ACPA response (defined as antibodies against CCP2, CEP-1, cFibβ36-52 and filaggrin) from the same time points, although at a lower frequency,” the authors noted.

Summary and Clinical Applicability

Antibody concentrations against antigen epitopes of the oral pathogen P gingivalis appear to increase prior to the onset of RA symptoms, suggesting that P gingivalis may be associated with RA pathogenesis.

Limitations

• Samples were collected from 2 separate population survey cohorts at irregular time intervals
• Result stratification according to ACPA status was not possible due to low numbers
• Inability to define a set cut-off value for anti-RgpB antibody response 

Reference

1. Johansson L, Sherina N, Kharlamova N, et al. Concentration of antibodies against Porphyromonas gingivalis is increased before the onset of symptoms of rheumatoid arthritis. Arthritis Res Ther. 2016;18:201.

follow @RheumAdvisor