Role of Periodontitis in the Development of CCP-Positive JIA

Juvenile idiopathic arthritis (JIA) is associated with extensive morbidity, including uveitis, joint damage, growth abnormalities, osteoporosis, and periodontal disease. The impact of JIA on oral health is significant, as evidenced by increased rates of dental caries, periodontal disease, and salivary abnormalities.¹  

The association between periodontitis and rheumatoid arthritis (RA) has been studied, with literature suggesting that citrullinated peptides produced by the periodontitis-causing bacteria Porphyromonas gingivalis may interfere with the normal immune system response to endogenous citrullinated antigens in genetically susceptible individuals.¹  To evaluate the prevalence of anti-P gingivalis antibodies in children with antibodies to cyclic citrullinated peptide (CCP), Lauren Lange, MD, and colleagues compared antibody titers in cohorts of children diagnosed with JIA.²

Children with JIA satisfying the International League of Associations for Rheumatology (ILAR) classification for JIA were studied, 77 of which were CCP-positive and 125 of which were CCP-negative. Serum antibodies against Prevotella intermedia, Fusobacterium nucleatum, and P gingivalis were measured in 71 children with CCP-positive JIA and 74 children with CCP-negative JIA. In addition, an oral health and smoke exposure questionnaire was completed by or on the behalf of 37 children with CCP-positive JIA and 121 children with CCP-negative JIA.

Anti-P gingivalis antibody concentrations were higher in the CCP-positive cohort compared to children with CCP-negative JIA (median antibody concentration 9.04 μg/mL vs 5.69 μg/mL; P <.001).  Log concentrations of anti-P intermedia antibody titers were also significantly higher in the CCP-positive cohort (5.4 ± 0.8 μg/mL vs 4.9 ± 1.0 μg/mL; P <.005). After adjusting for age differences between the groups using multivariable regression, anti-P gingivalis concentrations remained significant (P =.007). Log concentrations of antibodies to F nucleatum IgG did not differ between the 2 groups. 

Based on data from the oral health questionnaire, an increased prevalence of tender or bleeding gums was seen in the CCP-positive JIA cohort compared to the CCP-negative JIA cohort (43% vs 23%, P =.017). A higher prevalence of red/swollen gums was also seen in children with CCP-positive JIA compared to children with CCP-negative JIA (35% vs 20%, P =.055).

Thus, children with CCP-positive JIA demonstrate an increased antibody response to P gingivalis and P intermedia but not to F nucleatum compared to children with CCP-negative JIA. The authors of this study state that these findings “support the hypothesis that P gingivalis might play a role in the pathogenesis of CCP-positive JIA similar to RA.”

Summary and Clinical Applicability

Children with CCP-positive JIA have increased antibody responses to P gingivalis compared to children with CCP-negative JIA. This association suggests that pathogens implicated in periodontitis development may be involved in the development of CCP-positive disease.

Prevention of future disease morbidity is a goal of early disease identification and management. Physicians managing patients with JIA should encourage systematic dental management, placing emphasis on patient education, dietary recommendations, methods of plaque control, and the use of topical fluorides.¹

Reference

1.       Miranda LA, Fischer RG, Sztajnbok FR, Figueredo CM, Gustafsson A. Periodontal conditions in patients with juvenile idiopathic arthritis. J Clin Periodontol. 2003;30:969-974.

2.       Lange L, Thiele GM, McCracken C, et al. Symptoms of periodontitis and antibody responses to Porphyromonas gingivalis in juvenile idiopathic arthritis. Pediatr Rheumatol. 2016;14(1):8. doi: 10.1186%2Fs12969-016-0068-6.