Periodontal symptoms, immunometabolic factors and autoimmune diseases: A prospective cohort study

Periodontal health is increasingly recognized as an integral component of systemic homeostasis. However, whether its disruption contributes to the development of autoimmune diseases (ADs) remains unclear in prospective settings.

The aim of this study was to prospectively evaluate the association between periodontal symptoms and the risk of ADs, with particular attention to immunometabolic pathways and shared disease clusters.

A total of 465,454 participants from the UK Biobank were included. Cox proportional hazards models were employed to evaluate the association between periodontal symptoms and the incidence of 20 ADs. Sensitivity and subgroup analyses were conducted to assess the robustness of the results. Mediation analyses explored the potential mediating roles of 6 immunometabolic biomarkers. To address inter-disease correlations and reduce multicollinearity, factor analysis was applied to identify latent clusters of ADs.

During a median follow-up of 13.3 years, 33,895 participants developed at least 1 AD. Periodontal symptoms were linked to a higher risk of several ADs, with significant associations observed for bullous disorders, lichen planus, primary biliary cholangitis (PBC), and psoriasis. Mediation analyses revealed modest but statistically significant contributions of immunometabolic markers, particularly C-reactive protein (CRP). Factor analysis identified 3 AD clusters - autoantibody-mediated, autoimmune inflammatory and autoimmune metabolic diseases - all of which were significantly associated with poor periodontal health.

Periodontal symptoms were positively associated with multiple ADs and latent clusters, with these correlations being partly mediated by immunometabolic factors. The findings highlight the role of periodontal-systemic interactions in autoimmune pathogenesis.