Background/Purpose: Rheumatoid arthritis (RA) and periodontal disease (PD) are comorbid conditions that share multiple underlying risk factors and pathophysiological features. A dysbiotic periodontal microbiome might be an environmental trigger for RA, though the underlying mechanisms remain unclear. Several studies have focused on the ability of Porphyromonas gingivalis (Pg) to citrullinate human α-enolase, suggesting a direct relationship between periodontal bacteria and the development of serological autoimmunity, and possibly eventual autoimmune disease. We investigated the associations between 18 anti-citrullinated peptide antibodies (ACPAs) and antibodies to 18 species of periodontal bacteria in RA-free individuals with and without PD.

Methods: Adults with moderate to severe periodontal disease as defined by the 2000 American Academy of Periodontology definitions and no history of RA or RA symptoms were recruited for the PD group (n = 181). Periodontally healthy controls matched for age and sex were selected from the dental Atherosclerosis Risk in Communities (ARIC) cohort (n = 138). Serum anti-periodontal bacteria antibodies were measured using a rapid checkerboard immunoblotting technique. Analysis of ACPAs was performed using a multiplex assay platform. Linear regression models were used to examine the relationships between PD bacteria antibody titers and ACPA positivity while controlling for age, sex, and smoking status.

Results: Total number of ACPAs was equivalent between the PD and control groups, with 34% having at least one ACPA, and 7% having three or more ACPAs. For all but one PD bacterial species, antibody titers were significantly higher in the PD group compared to controls. Within the PD group, having a total of three or more ACPAs was generally associated with decreased anti-bacteria antibody titers including for Pg, Tannerella forsythia, and Treponema denticola (Td), though this reached statistical significance only with Td and marginally (p = 0.09). These trends were not seen with Prevotella species in the PD group, and were generally reduced or absent in the control group. Certain specific ACPAs were more strongly associated with decreased anti-bacterial antibody titers than others. Most notably, significantly decreased Td antibodies were associated with clusterin ACPA positivity (p < 0.05), and marginally with biglycan, fibrinogenA, and histone 2A ACPA positivity (all p-values < 0.10) in the PD group. Similar trends were seen with Pg across multiple ACPAs, and enolase across multiple bacterial species, but were generally weaker. There was no correlation between Pg antibody titers and enolase.

Conclusion: Relationships between ACPAs and PD bacteria antibody titers were predominantly inverse though largely not statistically significant in this small sample. The strongest relationships were found between distinct individual ACPAs and Td antibodies; results for Pg and enolase were relatively weak. Our results suggest an interplay between aberrant immune response to periodontal bacteria and serological autoimmunity, and have implications for future study of P. gingivalis and T. denticola as possible inciting factors of RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-periodontal-bacteria-antibody-titers-are-inversely-correlated-with-acpa-in-ra-free-individuals-with-periodontal-disease-compared-to-community-controls/