Date: Sunday, November 8, 2015
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Chronic periodontitis has been associated with rheumatoid arthritis (RA), and Porphyromonas gingivalis has been proposed as the mechanistic link, due to its unique property among pathogens to express a citrullinating enzyme (denoted P. PAD). We have recently demonstrated elevated anti-P. gingivalis antibody levels in patients with anti-citrullinated protein antibody (ACPA) positive RA compared to controls. To investigate this aetiological hypothesis further, we have analysed the anti-P. gingivalis antibody response in pre-RA individuals in relation to the development of the ACPA response.
Methods: Incident cases of RA were identified among participants (n=30447) in a community based health survey linked to local and national registers, followed by a structured review of the medical records. One control from the health survey, matched for age, sex and year of inclusion, was selected for each validated case. Anti-CCP2 antibody status was determined by the standard commercial ELISA method (Euro-Diagnostica AB). Anti-P. gingivalis IgG were detected by in-house ELISAs, using a citrullinated peptide derived from P. PAD (CPP3) and the arginine-containing equivalent (RPP3), or purified arginine gingipainB (RgpB) protein, as coating antigens. Cut off values for these antibodies were set at the 98th percentile among the controls. Analyses were stratified by time from inclusion in the health survey to RA diagnosis (1-5 and 6-13 years, respectively).
Serum was available from 166 cases (78% women), diagnosed with RA at a median of 5 years (IQR 3-8; range 1-13) after inclusion in the health survey. Anti-CPP3 and anti-RPP3 antibodies were detected in 6.0% and 5.4% of the pre-RA cases, respectively, whereas anti-CCP2 was positive in 22.3% of pre-RA cases. Positive anti-CPP3 antibodies were more frequent among anti-CCP2 antibody positive pre-RA cases (13.5 % vs. 3.9 %; p=0.04), whereas there was no such difference for anti-RPP3 IgG. Anti-CCP3 and anti-RPP3 antibodies occurred 1-5 years before RA diagnosis (7.2 % for both antibodies) as well as among those investigated 6-13 years before RA diagnosis (4.8% and 3.6%, respectively). Among anti-CPP3 positive pre-RA cases, levels of anti-CPP3 IgG were higher in those sampled ≤5 years before diagnosis (median 22.6 AU/ml (interquartile range (IQR) 17.0-29.2) vs. median 13.7 AU/ml (IQR 12.7-14.7; p=0.001), whereas there was no such difference for anti-RPP3 IgG (median 5.7 AU/ml; IQR 3.5-8.7 vs. median 4.2 AU/ml; IQR 3.9-14.6; p=0.71). Anti-RgpB IgG levels were not significantly different in pre-RA cases compared to controls (median 110.4 AU/ml;IQR 53.0-233.5 vs. median 94.4 AU/ml IQR 45.5-194.1; p=0.15).
Conclusion: Antibodies to P.gingivalis antigens occur years before RA diagnosis in a subset of pre-RA individuals. Presence of anti-CPP3 antibodies is associated with anti-CCP2 antibody positivity in the pre-clinical phase of RA, suggesting that the antibody response to citrullinated P.PAD in the context of chronic periodontitis could be one mechanism through which the early RA-specific immune phenotype can develop.
To cite this abstract in AMA style:Kharlamova N, Bergström U, Sherina N, Jacobsson LTH, Truedsson L, Lundberg K, Turesson C. Elevated Antibody Response to Porphyromonas Gingivalis Detected in Sera Years before the Clinical Onset of Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/elevated-antibody-response-to-porphyromonas-gingivalis-detected-in-sera-years-before-the-clinical-onset-of-rheumatoid-arthritis/. Accessed October 25, 2021.
« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/elevated-antibody-response-to-porphyromonas-gingivalis-detected-in-sera-years-before-the-clinical-onset-of-rheumatoid-arthritis/