Anti-cardiolipin and increased serum adhesion molecule levels in patients with aggressive periodontitis.

BACKGROUND: We observed that a significant proportion of patients with periodontitis have elevated serum levels of beta2-glycoprotein-I-dependent anti-cardiolipin (anti-CL). These prothrombotic autoantibodies, commonly found to be elevated in patients with systemic lupus erythematosus and the antiphospholipid syndrome, are associated with adverse pregnancy outcomes, such as fetal involution, prematurity, and low birth weight, and with cardiovascular sequelae, such as atherosclerosis, stroke, and myocardial infarction. Anti-CL is known to promote vascular inflammation and thrombosis. METHODS: We measured serum levels of markers of vascular inflammation, including soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cell adhesion molecule (sVCAM)-1, and sE-selectin, in 190 subjects with generalized aggressive or chronic periodontitis and in 90 periodontally healthy subjects. RESULTS: sVCAM-1 and sE-selectin levels were significantly higher in patients with elevated anti-CL (>15 U/ml). This relationship also was observed in the never-smoker subset of subjects, even after correction for demographic and periodontal variables. Within the diagnostic categories, sICAM-1, sVCAM-1, and sE-selectin were significantly higher in generalized aggressive periodontitis patients who had elevated anti-CL compared to those with normal anti-CL. Statistical correction for demographic and periodontal variables indicated that elevated anti-CL remained significantly associated with increased sVCAM-1 and sE-selectin in generalized aggressive periodontitis patients. CONCLUSIONS: Systemic markers of vascular inflammation in patients with aggressive periodontitis are associated with elevated levels of anti-CL. We hypothesize that a subset of periodontitis patients with elevated antiphospholipid antibodies could represent a subgroup at increased risk for obstetrical and cardiovascular sequelae.

Quantitative measures of aggressive periodontitis show substantial heritability and consistency with traditional diagnoses.

BACKGROUND: Aggressive periodontitis (AgP) research nearly always classifies subjects into traditional discrete categories of localized or generalized, based upon degree of attachment loss (AL) and types of affected teeth. Since AL is continuous and quantitative, however, useful information is lost. We developed quantitative measures of AgP, compared these to traditional methods, and estimated heritabilities in families. METHODS: We examined 237 healthy, 169 localized AgP, and 204 generalized AgP subjects. We used the site of maximum AL of each tooth to calculate means for each subject for different groups of teeth. We also applied principal components analysis (PCA) to condense variation among 28 teeth into three orthogonal (uncorrelated) variables. We used discriminant function analysis (DFA) to evaluate how well the quantitative measures match with traditional classifications. Quantitative trait heritabilities were estimated by variance components. RESULTS: PCA clustered first molars, incisors, and the other teeth into three groups. DFA showed that quantitative measures classified subjects consistent with traditional methods (87% to 94% agreement). Heritabilities ranged from 13.7% (P = 0.10) to 30.0% (P = 0.008) for quantitative measures, with highest values obtained for first molars. A combination of the principal component variables most heavily weighted on first molars and incisors gave the best model of disease susceptibility, with good separation of healthy versus diseased subjects, independent of disease extent or severity. CONCLUSIONS: Quantitative measures may provide improved precision and power for many kinds of periodontal research. Our finding of significant heritability supports their use in gene mapping studies of AgP susceptibility.

Locally produced anti-phosphorylcholine and anti-oxidized low-density lipoprotein antibodies in gingival crevicular fluid from aggressive periodontitis patients.

BACKGROUND: Sera from patients with periodontal attachment loss contain higher concentrations of IgG anti-phosphorylcholine (anti-PC) than sera from healthy subjects. Furthermore, a large proportion of plaque bacteria bear PC-containing surface antigens, implicating the oral flora as a source of immunogen for anti-PC. Additionally, anti-PC is cross-reactive with a variety of oral bacterial antigens and human antigens such as oxidized low-density lipoprotein (oxLDL). We hypothesized that, if the oral flora is a source of PC antigens, then we should be able to detect local anti-PC and anti-oxLDL production in gingival crevicular fluid (GCF). METHODS: To test this, we collected 66 GCF samples from 15 patients with aggressive periodontitis and examined both the GCF samples and serum samples for their content of IgG anti-PC, IgG anti-LDL, and IgG anti-oxLDL by enzyme-linked immunosorbent assay. We also determined levels of anti-tetanus toxoid (anti-TT) as a non-oral antigen control. Serum and GCF concentrations of serum albumin (HSA) were also determined for use as a dilution marker. A conservative GCF:serum antibody ratio of greater than 1.5 was considered to be evidence of local antibody production. RESULTS: For the non-oral antigen TT, only one out of 62 samples contained locally produced antibody. Eight out of 64 samples (7 from a single subject) demonstrated local production of anti-LDL. In contrast, 28 out of 66 samples demonstrated local production of anti-PC, and 47 out of 66 samples contained locally produced anti-oxLDL. It was observed that A. actinomycetemcomitans strains containing or devoid of PC could absorb anti-oxLDL from human sera. Although there was a correlation between the ratios of anti-PC and anti-oxLDL (Spearman's rho = 0.35, P = 0.0037), local production of both antibodies was found in only 17 out of 65 samples, indicating that these antibodies are not always reflective of reactivity to the same antigens. CONCLUSION: The local production of anti-PC and anti-oxLDL further implicates the oral flora as a source of antigen that may mediate immune reactions of relevance to cardiovascular and other systemic diseases.