Associations of Antibodies Targeting Periodontal Pathogens With Subclinical Coronary, Carotid, and Peripheral Arterial Atherosclerosis in Rheumatoid Arthritis

Abstract

Objective. Both periodontal disease and cardiovascular disease (CVD) are overrepresented in rheumatoid arthritis (RA). This study was undertaken to investigate the contribution of periodontal pathogens to CVD in RA. Methods. RA patients underwent assessments of coronary artery calcification (CAC), carotid intima-media thickness and plaque, and ankle-brachial index via computed tomography, ultrasound, and Doppler ultrasound, respectively. Sera were assayed for antibodies targeting Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans serotype B (Aa), and Aa-derived leukotoxin A (LtxA). Associations of antibodies against these periodontal pathogens with measures of atherosclerosis were explored using generalized linear models. Results. Among 197 RA patients, anti-Pg was detected in 72 patients (37%), anti-Aa in 41 patients (21%), and anti-LtxA in 84 patients (43%). Adjusting for relevant confounders and reported tooth loss, the mean CAC score was 90% higher in those with anti-Aa and/or anti-LtxA compared with those without either antibody (19 units versus 10 units; P = 0.033). The adjusted odds of CAC ≥100 units were 2.23-fold higher in those with anti-Aa and/or anti-LtxA compared with those without either antibody (P = 0.040). Anti-Aa and/or anti-LtxA seropositivity was significantly associated with all other assessed measures of atherosclerosis except carotid plaque. Anti-Pg was not associated with any measure of atherosclerosis. Higher swollen joint count was associated with CAC exclusively in the group with anti-Aa and/or anti-LtxA. Conclusion. Immunoreactivity against Aa and/or its major virulence factor LtxA was associated with atherosclerosis in multiple vascular beds of RA patients and amplified the effect of swollen joints on coronary atherosclerosis, suggesting a role for treatment/prevention of periodontal disease in the prevention of CVD in RA.

Association Between Serum Thyroid-Stimulating Hormone Levels and Salivary Microbiome Shifts

“…Porphyromonas is a key pathogen in periodontitis and is closely related to many systemic diseases. A number of studies have explored the role of Porphyromonas in atherosclerosis (Giles et al, 2020), Alzheimer's disease (Miller and Scott, 2020), rheumatoid arthritis (Cheng et al, 2020), diabetes (Minty et al, 2019), and adverse pregnancy outcomes (Chopra et al, 2020) and nonalcoholic fatty liver disease (Clos-Garcia et al, 2020;Wang et al, 2020;Zhou et al, 2020). Parvimonas have been reported to be a potential carcinogenic pathogen, which is positively associated with oral squamous cell carcinoma (OSCC) (Zhou et al, 2020), colorectal cancer (Clos-Garcia et al, 2020), and gastric cancer (Gantuya et al, 2020).…”

The Association of Periodontitis and Peripheral Arterial Occlusive Disease in a Prospective Population-Based Cross-Sectional Cohort Study

“…Four different mechanisms were previously discussed [ 28 ]. Periodontal bacteria enter the bloodstream or spread over the lymphatic system and invade the arterial wall, causing initiation of arteriosclerosis [ 29 ]. Inflammatory mediators (Interleukin-6 and tumor-necrosis factor α) reaches the liver through the blood stream and induce an increased production of CRP and fibrinogen.…”

“…Periodontal bacteria enter the bloodstream or spread over the lymphatic system and invade the arterial wall, causing initiation of arteriosclerosis [ 29 ].…”

Causal risk and protective factors in rheumatoid arthritis: A genetic update

“…The development of IgM antibodies against A. actinomycetemcomitans leukotoxin A (AaLtxA) is retrieved with RA at early disease stage (OR = 1.012; CI95: 1.007–1.017) and elevated levels are maintained after adjustment with ACPA/RF status, tobacco smoking, sex, and HLA-DRB1 shared epitope (SE) [ 54 ]. When present in patients with RA, IgG anti-Aa and/or anti-AaLtxA antibodies, but not IgG anti-Pg antibodies, are associated with a higher prevalence of RF and atherosclerosis in those patients with higher swollen joint counts [ 55 ]. Of note, the increase citrullinisation and PADI2/4 expression observed in gingival tissues from RA patients with periodontitis is imperfectly associated with P. gingivalis and A. actinomycetemcomitans detection, which suggests other factors implicated in PAD2/4 overexpression and neo-epitope formation [ 56 ].…”