Can Periodontal Antigen Antibodies Be Predictive of Clinical Responses to bDMARDs in RA?

Serum immunoglobulin levels against the periodontal antigen Porphyromonas gingivalis peptidylarginine deiminase appear to correlate with the clinical responses to bDMARD therapy in RA

Serum immunoglobulin G (IgG) levels against the periodontal antigen Porphyromonas gingivalis peptidylarginine deiminase (PPAD) appear to correlate with clinical responses to biologic disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA).

Porphyromonas ginigivalis, a common periodontal pathogen, is increasingly recognized as having a role in the production of anti-cyclic citrullinated peptide (CCP) IgGs, which in turn may influence RA pathogenesis. Determining serum PPAD antibody titers may help predict clinical responses to bDMARDs in patients with RA.

Tetsuo Kobayashi of Niigata University Medical and Dental Hospital, Niigata, Japan, and colleagues, retrospectively analyzed 60 patients with RA at a single center in Japan who had been previously taken conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) who were then treated with a bDMARD between July 2011 and January 2015.

Study participants underwent independent, blinded rheumatologic and periodontal evaluations at baseline (pre-treatment assessment) then at 3 and 6 months after first bDMARD dose. Disease Activity Score including 28 joints using C-reactive protein (DAS28-CRP), tender and swollen joint counts, disease duration, and the patient’s self assessment of own condition were evaluated in addition to recording gingival index, bleeding on probing, O’Leary’s plaque control record, number of teeth present, and clinical tooth attachment level.

Enzyme-linked immunosorbant assays were used to determine serum levels of anti-PPAD IgG.  Blood samples were then analyzed for 8 functional RA-associated single nucleotide polymorphisms (SNPs) in genomic DNA. 

Researchers found that study participants with low titers of anti-PPAD IgG had decreased improvements in DAS28-CRP after 3 and 6 months of bDMARD treatment as compared to patients with high anti-PPAD titers (P=.04 for both months). 

Participants with low anti-CCP IgG titers also were also found to have decreased improvements in DAS28-CRP after 3 and 6 months of bDMARD treatment when compared to those with higher titers (P=.03 and P=.04, respectively).

After adjusting for age, gender, smoking, periodontal condition, and SNPs in multiple regression analyses, a positive association was found between anti-PPAD IgG titers and DAS28-CRP changes after bDMARD treatment for 6 months (P=.0006).

Summary and Clinical Applicability

The presence of PPAD IgG was associated with improvements in disease activity scores in patients with RA previously treated with csDMARD therapy at baseline who then received 6 months of bDMARD therapy.

“Determination of the serum anti-PPAD IgG titers might help in designing a new personalized treatment strategy for RA”, the authors concluded.

Limitations and Disclosures

This study was limited by the exclusion of patients with high RA disease activity that had already been started on bDMARD therapy, limiting the evaluation of responses to bDMARD therapy due to the smaller sample sizes.  The inherent selection bias associated with retrospective cohort studies has to be considered. 

“[Further] caution is necessary when the interpreting the present data due to the long period of time since the patients were initially diagnosed with RA. It might be promising to evaluate the response for a longer period from soon after RA diagnosis to determine a reliable predictor for the efficacy of bDMARD therapy,” the authors noted. 

This study was supported by the Japan Society for the Promotion of Science 


Kobayashi T, Ito S, Kobayashi D, et al. Serum Immunoglobulin G Levels to Porphyromonas gingivalis Peptidylarginine Deiminase Affect Clinical Response to Biological Disease-Modifying Antirheumatic Drug in Rheumatoid Arthritis. PLoS ONE. 2016;11(4):e0154182.