Antibodies to Porphyromonas gingivalis Indicate Interaction Between Oral Infection, Smoking, and Risk Genes in Rheumatoid Arthritis Etiology

Abstract

Objectives To investigate the role of the periodontal pathogen Porphyromonas gingivalis in rheumatoid arthritis (RA) etiology, we have analysed the antibody response to P. gingivalis virulence factor arginine gingipainB (RgpB) in relation to anti-citrullinated protein antibodies (ACPA), smoking and HLA-DRB1 shared epitope (SE) alleles, in patients with periodontitis (PD) and RA, and in controls. Methods Anti-RgpB IgG was measured by ELISA in 65 PD patients and 59 non-PD controls, and in 1,975 RA cases and 377 non-RA controls from the Swedish population-based case-control study EIRA (Epidemiological Investigation of RA). Autoantibody status, smoking habits and genetic data were retrieved from the EIRA database. Differences in antibody levels were examined using Mann-Whitney U test. Unconditional logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI) for the association of anti-RgpB IgG with different RA subsets. Results Anti-RgpB antibody levels were significantly elevated in PD compared to non-PD; in RA compared to non-RA; and in ACPA-positive RA compared to ACPA-negative RA. There was a significant association between anti-RgpB IgG and RA (OR=2.96; 95% CI: 2.00–4.37), which was even stronger than the association between smoking and RA (OR=1.37; 95% CI: 1.07–1.74), and in ACPA-positive RA, there were interactions between anti-RgpB antibodies and both smoking and SE. Conclusion Our study suggests that the previously reported link between PD and RA could be accounted for by P. gingivalis infection, and we conclude that P. gingivalis is a credible candidate for triggering and/or driving autoimmunity and autoimmune disease in a subset of RA.

Association between oral lesions and disease activity in lupus erythematosus

“…Oral ulcers in the setting of SLE have long been considered to be predictors of systemic vasculitis and worse prognosis. 42 As mentioned above, oral and nasal ulcers are considered as clinical criterion for SLE in the SLICC classification system. 25,30,40 To date, oral ulcers have not been associated with nephritis, 24,25 with vasculitis 24,25,40 or with a significant change in serum levels of anti-dsDNA antibodies, ANA or complement.…”

Bone loss and aggravated autoimmune arthritis in HLA-DRβ1-bearing humanized mice following oral challenge with Porphyromonas gingivalis

“…We have circumvented this problem by generating an I-A°/I-E° mouse on the C57BL/6 background that expresses a chimeric mouse/human RA susceptibility allele HLA-DR1(*0101) as a transgene. Recent research has suggested that this same DR1 restriction element may also serve as a susceptibility allele for periodontal disease [24, 25], providing a unique opportunity for use as an animal model that is perfectly suited for the analysis of linkages between the two disease processes. While there has been one study in which HLA-DR4 tg mice were used to look at the role of citrullinated human α-enolase [11], to our knowledge no HLA-DR1 mice have been challenged with P. gingivalis to assess its role in ACPA development or modulation of arthritis.…”

Problems of Rheumatoid Arthritis Immunopathology: Evolution of the Disease

“…При РА обнаружен феномен аутоцитруллинирования ПАД P. gingivalis, ведущий к образованию антител к ПАД [149], который, однако, не характерен для «преклиниче-ской» фазы РА [150]. В то же время данные эпидемиологи-ческих исследований не подтверждают связь между пе-риодонтитом и РА [151], хотя антитела, специфичные к P. gingivalis, обнаруживаются в сыворотках АЦБ-пози-тивных пациентов с РА [152]. Более того, недавно было показано, что у млекопитающих кальций-зависимая ПАД цитруллинирует специфические аргининовые остатки внутри полипептидной цепи молекулы белка (эндоцит-руллинирование), в то время как ПАД P. gingivalis модифи-цирует только С-терминальный аргинин [153].…”