Date: Sunday, November 8, 2015
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: It has been hypothesized that Porphyromonas gingivalis – the only known pathogen to express a citrullinating enzyme (called P.PAD) – is etiologically linked to the development of anti-citrullinated protein antibody (ACPA) positive RA, via citrullination of its own as well as human proteins, generating autoantigens and the subsequent production of ACPA. In support of this hypothesis, it was recently shown that P.PAD can auto-citrullinate and that a subset of RA patients has elevated antibody levels towards citrullinated P.PAD. In the present study, we have characterized this antibody response in more details.
Methods: The antibody response to a citrullinated P.PAD-derived peptide denoted CPP3 (and the arginine-containing equivalent RPP3) was analysed in the Swedish population-based case-control cohort EIRA (n=2,859 RA cases; n=373 controls) using the ImmunoCAP ISAC microarray system (PhaDia Multiplexing Diagnostics). ACPA status, smoking habits, genetics, CRP levels and DAS28 data were retrieved from the EIRA database. Unconditional logistic regression analysis was used to calculate odds ratios (OR) with 95% confidence intervals (CI) for the association of different risk factors with different RA subsets.
With 98% specificity, using the EIRA control population to set cut-off, 10.4% of EIRA RA cases had antibodies to CPP3, and interestingly, 5.4% had antibodies to RPP3. In the same cohort, 65% were anti-CCP2 antibody positive. The majority of anti-CPP3 antibody positive patients were confined to the CCP2 positive population, and anti-CPP3 antibody levels correlated strongly with other ACPA fine-specificity levels (r = 0,99; p ˂ 0,0001). When comparing CCP2+ / CPP3+ patients with CCP2+ / CPP3- patients, a significantly stronger association was found between smoking and the double positive subset (OR=2.88; 95% CI: 2.11-3.92) than between smoking and the CCP2 single positive subset (OR=1.75; 95% CI: 1.54-1.99) (p<0.0012), while we could not detect any significant difference with respect to the association of HLA-DRB1 shared epitope and the two different subsets of RA (OR=7.27; 95% CI: 4.82-10.97 and OR=5.52; 95% CI: 4.58-6.64, for CCP2+ / CPP3+ and CCP2+ / CPP3- RA, respectively, p=0.32). As with the ACPA response in general, there was only a weak correlation between anti-CPP3 antibody positivity and baseline DAS28 and CRP levels.
Conclusions: A small subset of RA (10.4%), mainly anti-CCP2+ RA, had an antibody response to CPP3. This antibody response associated with the ACPA response and showed similar characteristics as other ACPA fine-specificities, in relation to RA risk factors and disease activity scores. However, a subset of RA patients also had an antibody response to the arginine-containing RPP3 peptide (5.4%), which is not the case for most arginine-containing epitopes. Contrary to the other ACPA targets, CPP3 is a bacterial peptide sequence, and in a subset of patients, this antibody response could represent an aetiological link between P. gingivalis infection and ACPA+ RA development.
To cite this abstract in AMA style:Kharlamova N, Jiang X, Sherina N, Hansson M, Lundberg K, Alfredsson L. Characterisation of the Antibody Response to a Citrullinated Peptide – Derived from the Porphyromonas Gingivalis Peptidyl Arginine Deiminase Enzyme – in Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/characterisation-of-the-antibody-response-to-a-citrullinated-peptide-derived-from-the-porphyromonas-gingivalis-peptidyl-arginine-deiminase-enzyme-in-patients-with-rheumatoid-arthritis/. Accessed May 17, 2022.
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