Carol N. Brooks

IL-17 in Sera from Patients with Aggressive Periodontitis

Interleukin-17 (IL-17), the prototype cytokine produced by the Th17 subset of T-helper cells, plays a role in inflammatory responses, autoimmunity, and antimicrobial responses in a variety of infectious and inflammatory diseases. In view of the inflammatory nature and severity of aggressive periodontitis, we hypothesized that IL-17 might be detected in sera from patients with aggressive periodontitis. We used ELISA to measure IL-17 serum concentrations from 67 periodontally healthy (NP) individuals and from 53 patients with localized (LAgP) and 49 patients with generalized (GAgP) aggressive periodontitis. IL-17 was barely detectable in sera from periodontally healthy individuals (1.9 ± 2.0 pg/mL), but was present at significantly higher concentrations in sera from those with LAgP (7.6 ± 2.2 pg/mL) and GAgP (17.1 ± 2.3 pg/mL). Multivariate analyses demonstrated associations of IL-17 concentrations with periodontal attachment loss, but not with current smoking. Therefore, Th17 responses may be characteristic of AgP, and IL-17 may play a role in the pathogenesis of aggressive periodontitis.

Anti-cardiolipin Antibodies in Sera from Patients with Periodontitis

Antiphospholipid antibodies are commonly found in patients with systemic lupus erythematosus or the antiphospholipid syndrome, and a subset of such antibodies is associated with prothrombotic events such as stroke and with adverse pregnancy outcomes and fetal loss. We examined sera from 411 patients who were clinically characterized as to their periodontal disease status for serum levels of β2-glycoprotein I-dependent anti-cardiolipin autoantibodies (anti-CL). The prevalence of patients with chronic periodontitis (CP) and generalized aggressive periodontitis (GAgP) positive for anti-CL (16.2% and 19.3%, respectively) was greater than that in healthy controls (NP) and localized aggressive periodontitis (LAgP) patients (6.8% and 3.2%). Patients with these autoantibodies demonstrated increased pocket depth and attachment loss compared with patients lacking the antibodies. Analysis of the data indicates that patients with generalized periodontitis have elevated levels of autoantibodies reactive with phospholipids. These antibodies could be involved in elevated risk for stroke, atherosclerosis, or pre-term birth in periodontitis patients.

Phosphorylcholine-Dependent Cross-Reactivity between Dental Plaque Bacteria and Oxidized Low-Density Lipoproteins

ABSTRACT Antibodies reactive with phosphorylcholine (PC) are ubiquitous in human sera, but the antigens stimulating their production and their function are not clear. Previous studies have shown that a significant proportion of dental plaque bacteria contain PC as determined by reactivity with PC-specific mouse myeloma proteins and monoclonal antibodies. Additionally, serum antibody concentrations of immunoglobulin (IgG) G anti-PC are higher in sera of individuals who have experienced periodontal attachment loss than those who are periodontally healthy. These data implicate the oral microflora as a source of antigen-stimulating anti-PC responses. Recent data also indicate that antibodies with specificity for PC are elevated in ApoE-deficient mice, a model for studies of athersclerosis, and that such antibodies bound oxidized low-density lipoproteins (LDL) (oxLDL) in atherosclerotic plaques. These data prompted the hypothesis that human anti-PC could bind to both oral bacteria and human oxLDL, and that these antigens are cross-reactive. We therefore examined the ability of human anti-PC to bind to PC-bearing strains of oral bacteria using enzyme-linked immunosorbent inhibition assays and by assessment of direct binding of affinity-purified human anti-PC to PC-bearingActinobacillus actinomycetemcomitans. Our results indicated that PC-bearing strains of Streptococcus oralis,Streptococcus sanguis, Haemophilus aphrophilus,Actinomyces naeslundii, Fusobacterium nucleatum, and A. actinomycetemcomitans, as well as a strain of Streptococcus pneumoniae, absorbed up to 80% of anti-PC IgG antibody from human sera. Furthermore, purified anti-PC bound to a PC-bearing strain of A. actinomycetemcomitansbut only poorly to a PC-negative strain. OxLDL also absorbed anti-PC from human sera, and oxLDL but not LDL reacted with up to 80% of the anti-PC in human sera. Furthermore, purified anti-PC bound directly to oxLDL but not to LDL. The data indicate that PC-containing antigens on a variety of common oral bacteria are cross-reactive with neoantigens expressed in oxLDL. We propose that PC-bearing dental plaque microorganisms may induce an antibody response to PC that could influence the inflammatory response associated with atherosclerosis.

Evidence of a Substantial Genetic Basis for IgG2 Levels in Families with Aggressive Periodontitis

IgG2 is elevated in localized but not in generalized aggressive periodontitis (AgP). Exposure to pathogenic bacteria is essential for disease. Immune responses are dominated by IgG2 reactive with bacterial surface carbohydrates. We used variance component analyses to assess IgG2 heritability and determine whether genes that influence IgG2 are the same genes that influence disease susceptibility. We studied 17 Caucasian and 43 African American families with two or more localized or generalized AgP-affected members (274 subjects with IgG2 measurements). Only 16% of the variance in IgG2 was attributable to age, race, and smoking. Even with the addition of localized AgP, the model still explained only 19% of IgG2 variance. By contrast, heritability of IgG2 levels was estimated to be 38% and highly significant (P = 0.0006), demonstrating a substantial genetic basis. Bi-trait variance component analyses of IgG2 and quantitative measures of AgP indicate that different genes appear to control IgG2 levels and disease susceptibility.

Anti-cardiolipin from periodontitis patients induces MCP-1 production by human umbilical vein endothelial cells.

AIM Periodontal diseases are associated with a variety of systemic diseases, including cardiovascular disease and stroke, and patients with periodontitis demonstrate elevated levels of anti-cardiolipin antibodies. We sought to determine if anti-cardiolipin antibodies from periodontitis patients induced monocyte chemotactic protein-1 production by human vascular endothelial cells. MATERIALS AND METHODS IgG was purified from sera from 53 subjects, including chronic and aggressive periodontitis patients and periodontally healthy controls, with elevated or normal IgG anti-cardiolipin levels. In addition, anti-cardiolipin antibodies were specifically removed from some sera by immunoabsorption. RESULTS We found that, irrespective of diagnostic category, IgG from subjects with elevated anti-cardiolipin induced significantly greater monocyte chemotactic protein-1 production by human vascular endothelial cells than IgG from those subjects with normal anti-cardiolipin titres. Removal of anti-cardiolipin from IgG preparations from periodontitis patients significantly reduced their ability to induce monocyte chemotactic protein-1. CONCLUSIONS Since elevated titres of anti-cardiolipin are found in a significantly greater proportion of patients with periodontitis than in periodontally healthy individuals, and these antibodies activate endothelial cells to produce monocyte chemotactic protein-1, they may explain some of the associations noted between periodontal infections and systemic conditions.

Serum Anticardiolipin Concentrations in Patients With Chronic Periodontitis Following Scaling and Root Planing

BACKGROUND Anticardiolipin antibodies (antiCl), present in some patients with autoimmune disease, are associated with thrombosis, fetal loss, and other conditions. A significant proportion of patients with chronic periodontitis (CP) test positive for antiCl, likely because some periodontal pathogens contain antigens homologous to the target antigen of antiCl on the serum protein β-2 glycoprotein-I (β2GPI) and thus can induce antiCl by molecular mimicry. The authors hypothesized that treatment of periodontitis by scaling and root planing (SRP) could therefore decrease serum titers of antiCl in patients with CP. METHODS Thirty patients with CP received complete periodontal examinations at baseline including assessment of probing depth, attachment loss, gingival index, and plaque index. SRP was performed in two sessions at 2-week intervals. Eight weeks later, patients were reexamined. Blood samples were taken at baseline, 2 weeks after the initial therapy appointment, and 8 weeks after the completion of treatment for assessment of immunoglobulin (Ig)G and IgM antiCl levels. RESULTS All periodontal parameters improved significantly. Consistent with previous observations, five (16.7%) of the 30 patients exhibited elevated levels of IgG or IgM antiCl at baseline. Following treatment, the concentrations of IgG and IgM antiCl remained unchanged for the entire cohort of 30 patients. However, in the five patients with elevated antiCl at baseline, IgM antiCl concentrations decreased significantly (P = 0.0008) owing to therapy, while IgG antiCl did not. CONCLUSION The oral microflora is a likely source of antigen inducing antiCl in CP, since IgM antiCl levels can be reduced in the short term with conservative therapy.