Session Title: Rheumatoid Arthritis: Human Etiology and Pathogenesis II
Session Type: Abstract Submissions (ACR)
Background/Purpose: Rheumatoid arthritis (RA) is characterized by the production of autoantibodies to citrullinated proteins (ACPA). Citrullinated proteins are generated by the actions of peptidyl arginine deminase (PAD) enzymes during inflammation. Since ACPA can be detected prior to joint symptoms develop, it has been suggested that citrullination and break of tolerance to citrullinated proteins may be triggered outside the joint, potentially at mucosal surfaces. We hypothesize that Porphyromonas gingivalis, a major cause of chronic periodontitis (PD) and the only known pathogen to express PAD (P.PAD), is etiologically involved in the development of ACPA+ RA. We (Quirke, Potempa and Venables) have recently shown that autocitrullinated P.PAD is targeted by antibodies in RA, while arginine gingipain (another P. gingivalis-specific protein) is not. We have now investigated these antibody responses in more detail, with an aim to develop a serological test for diagnosing PD and to elucidate the potential link between PD and RA.
Methods: In-house ELISA assays, based on five different citrullinated P.PAD peptides (CPP3, 5, 6, 8 and 10), one arginine-containing control peptide (RPP3) and recombinant arginine gingipain protein (RgpB) were used to examine IgG responses in serum from: 102 ACPA+ RA cases; 98 ACPA- RA cases; 100 non-RA controls; 66 patients with confirmed PD; and 60 non-PD controls (confirmed by dentist). Mann-Whitney U-test for independent groups was used to determine statistical differences.
Results: The anti-CPP3 IgG response associated only, strongly and significantly with ACPA+ RA, while no antibody response was recorded towards RPP3. Also anti-CPP6 and 8 IgG showed similar association with ACPA+ RA, while the anti-CPP5 response also associated with confirmed PD (fig 1A). No anti-CPP10 IgG response could be detected in any subgroup. The antibody response towards RgpB associated mainly and significantly with confirmed PD. Compared to non-PD controls, anti-RgpB IgG levels were also increased in ACPA+ RA, ACPA- RA and non-RA controls, although no statistical significance could be detected between the groups (fig 1B).
Conclusion: Based on these results, anti-RgpB IgG could potentially be used as a serological marker to identify PD-cases retrospectively. This would be of great help when investigating the etiological link between PD and RA, or PD and other inflammatory diseases, since validated information on periodontal status is often lacking, while serum cohorts are available. The antibody-response to citrullinated P.PAD in RA could be confirmed and evaluated in more detail. This antibody response was confined to ACPA+ RA and specific epitopes, where CPP5 was particularly interesting as antibodies associated with both ACPA+ RA and PD, supporting the hypothesis that PD/P. gingivalis may be causatively linked to the development of ACPA+ RA.
A. M. Quirke,
« Back to 2013 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/antibodies-to-porphyromonas-gingivalis-as-an-etiological-clue-to-the-development-of-anti-citrullinated-protein-antibody-positive-rheumatoid-arthritis/