Influence of periodontitis on levels of autoantibodies in rheumatoid arthritis patients: A systematic review

Abstract

Background and objective: Periodontitis (PD) is a dysbiotic disease of tooth-supporting structures that has been associated with various systemic diseases including rheumatoid arthritis (RA). To date, evidence demonstrated increased prevalence of RA among PD patients and postulated PD to have a role in the development of autoantibodies in RA patients. Therefore, a systematic review was conducted to assess the available evidence to ascertain the effect of PD on levels of autoantibodies in the serum, saliva and gingival crevicular fluid (GCF) of RA patients. Material and methods: The systematic review was conducted in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. Relevant literature was searched from PubMed, Web of Science, Scopus and Ebscohost databases from inception until 31 August 2020. The risk of bias in each study was determined based on the Newcastle-Ottawa Scale tool. Resultsfrom random-effect meta-analyses were presented as summary estimates of odds ratios (ORs) for seropositivity and standardised mean difference (SMD) of autoantibody levels with 95% confidence intervals. Sensitivity tests and meta-regression were performed to assess the robustness of the results and potential cause of heterogeneity. Results:The electronic and manual searches gathered 932 articles. Following screening and full-text assessment, a total of 29 studies were included in the analysis. Twentyeight published observational studies were included in the quantitative analysis in the form of random-effect meta-analysis which revealed that PD was associated with anticitrullinated proteins autoantibodies (ACPAs) and Rheumatoid Factor (RF) seropositive RA patients (OR for ACPA seropositivity: 1.82; 95% CI: 1.13-2.93) (OR for RF seropositivity: 1.53; 95% CI: 1.05-2.24). Also, RA patients with PD had increased serum levels of ACPA and RF. However, high heterogeneity among studies' results, partially ascribed to the unstandardised case definition of PD and laboratory testing of autoantibodies.Apart from ACPA and RF in serum, studies which reported on other RA-related autoantibodies, as well as autoantibody levels in saliva and GCF were scarce. Conclusion:RA patients with PD tend to have greater ACPA and RF levels in their serum when compared with the RA patients without PD supporting the plausible role of PD in the development of systemic autoimmunity in RA patients.

Salivary and serum levels of neutrophil proteases in periodontitis and rheumatoid arthritis

“…and the medication status of the participants. The production of autoantibodies is one plausible mechanism in the relationship between RA and periodontitis (Eezammuddeen et al, 2022) may explain the present findings. It is known that the autoantibodies increase the levels of neutrophil proteases in serum and synovial fluids (Koziel & Potempa, 2022).…”

Higher odds of periodontitis in systemic lupus erythematosus compared to controls and rheumatoid arthritis: a systematic review, meta-analysis and network meta-analysis

“…Prolonged exposure to citrullinated proteins in the oral cavity may trigger the production of anti-cyclic citrullinated peptide (CCP) antibodies, potentially leading to the onset of RA in susceptible individuals ( 23 ). The associations between (i) periodontitis and anti-CCP seropositivity and (ii) periodontitis severity and presence of anti-CCP antibodies in patients with RA provide further support for this hypothesis ( 24 , 25 ). In addition, disease-modifying antirheumatic drugs ameliorate both RA and periodontitis, suggesting shared inflammatory pathways ( 26 ).…”

Neutrophil extracellular traps in rheumatoid arthritis and periodontitis: Contribution of PADI4 gene polymorphisms

“…RA and periodontitis are chronic inflammatory diseases defined, respectively, by the destruction of articular cartilage and of tooth-supporting periodontal tissues, which can lead to systemic repercussions and tooth loss (González-Febles & Sanz, 2021;Potempa et al, 2017). Despite the differences in the etiopathogenesis of RA and periodontitis, cross-talk of the diseases occurs through inflammatory mediators and anti-citrullinated protein antibodies (ACPAs) (Eezammuddeen et al, 2023). Citrullination is a post-translational modification that can be caused by periodontopathogenic bacteria such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans (Eezammuddeen et al, 2023;G omez-Bañuelos et al, 2019;González-Febles & Sanz, 2021;Shimada et al, 2016).…”

“…Despite the differences in the etiopathogenesis of RA and periodontitis, cross‐talk of the diseases occurs through inflammatory mediators and anti‐citrullinated protein antibodies (ACPAs) (Eezammuddeen et al, 2023). Citrullination is a post‐translational modification that can be caused by periodontopathogenic bacteria such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans (Eezammuddeen et al, 2023; Gómez‐Bañuelos et al, 2019; González‐Febles & Sanz, 2021; Shimada et al, 2016). The presence of these bacteria in periodontal pockets has been associated with increased ACPA production (Gómez‐Bañuelos et al, 2019; Shimada et al, 2016).…”