Periodontitis in pregnant baboons: systemic inflammation and adaptive immune responses and pregnancy outcomes in a baboon model.

BACKGROUND/OBJECTIVES: Chronic periodontal infections have been suggested to contribute to the risk of adverse pregnancy outcomes. MATERIAL AND METHODS: This study describes the relationship of patterns of systemic inflammatory mediators and IgG antibody to 20 oral bacteria in pregnant female baboons (Papio anubis) coupled with clinical features of ligature-induced periodontitis, as risk indicators for adverse pregnancy outcomes. Animals showing a preterm delivery and/or low birth weight newborns, as well as those pregnancies resulting in spontaneous abortion, stillbirth, or fetal demise were tabulated as adverse pregnancy outcomes. RESULTS: A significantly greater frequency of the periodontitis group neonates had a low birth weight (18.1%; p = 0.008) and decreased gestational age (9.8%). Spontaneous abortion/stillbirth/fetal demise were increased in the periodontitis (8.7%) versus the control group (3.8%) (p = 0.054). The baseline oral clinical presentation of the experimental animals did not relate to the adverse pregnancy outcomes. Animals with the greatest extent/severity of periodontitis progression during the initial ½ of gestation (ie. to mid-pregnancy) had the greatest risk for adverse pregnancy outcomes. Baseline biological parameters indicating historical responses of the animals to periodontal challenge demonstrated individual variation in selected mediators, some of which became more differential during ligature-induced periodontitis. The relationship of clinical parameters to systemic inflammatory responses was consistent with a temporal contribution to adverse pregnancy outcomes in a subset of the animals. CONCLUSIONS: These results support a link between periodontitis and adverse pregnancy outcomes in the baboons and provide a prospective experimental model for delineating the biologic parameters that contribute to a causal relationship between chronic oral infections and birth events.

Systemic inflammatory responses in progressing periodontitis during pregnancy in a baboon model.

This study tested the hypothesis that pregnant female baboons exhibit increased levels of various inflammatory mediators in serum resulting from ligature-induced periodontitis, and that these profiles would relate to periodontal disease severity/extent in the animals. The animals were sampled at baseline (B), mid-pregnancy (MP; two quadrants ligated) and at delivery (D; four quadrants ligated). All baboons developed increased plaque, gingival inflammation and bleeding, pocket depths and attachment loss following placement of the ligatures. By MP, both prostaglandin E(2) (PGE(2)) and bactericidal permeability inducing factor (BPI) were greater than baseline, while increased levels of interleukin (IL)-6 occurred in the experimental animals by the time of delivery. IL-8, MCP-1 and LBP all decreased from baseline through the ligation phase of the study. Stratification of the animals by baseline clinical presentation demonstrated that PGE(2), LBP, IL-8 and MCP-1 levels were altered throughout the ligation interval, irrespective of baseline clinical values. IL-6, IL-8 and LBP were significantly lower in the subset of animals that demonstrated the least clinical response to ligation, indicative of progressing periodontal disease. PGE(2), macrophage chemotactic protein (MCP)-1, regulated upon activation, normal T cell expressed and secreted (RANTES) and LBP were decreased in the most diseased subset of animals at delivery. Systemic antibody responses to Fusobacterium nucleatum, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Campylobacter rectus were associated most frequently with variations in inflammatory mediator levels. These results provide a profile of systemic inflammatory mediators during ligature-induced periodontitis in pregnant baboons. The relationship of the oral clinical parameters to systemic inflammatory responses is consistent with a contribution to adverse pregnancy outcomes in a subset of the animals.

Differences in pediatric dental services under general anesthesia for Medicaid and military dependent children.

PURPOSE: This study's purpose was to compare pediatric dental services provided for Medicaid and military dependent children to determine if differences in dental treatment choices exist based on site and payment method. METHODS: Subjects included 120 Medicaid patients at the University of Texas Health Science Center at San Antonio and 120 military dependents at Lackland Air Force Base, Texas. Demographic data and treatment information were abstracted for children younger than 6 years old receiving dental treatment under general anesthesia between 2002 and 2006. Data was analyzed using Wilcoxon rank sum, Kruskal-Wallis, and Fisher's exact tests. RESULTS: The Medicaid recipients were younger (40.2 vs 49.8 months, P<.001) and more likely to be Hispanic (78% vs 30%, P<.001). The means of decayed teeth, fillings, and stainless steel crowns did not differ between sites. Medicaid children received more composite fillings (P<.001), fewer amalgam fillings (P<.001), fewer pulp therapies (P<.001), more extractions (P=.01), and fewer sealants (P<.001). Age and gender did not affect decay rates, but those of Hispanic ethnicity did experience more decay than non-Hispanics (9.5 vs 8.6, P=.02). CONCLUSION: This study found no difference in the number of less conservative, albeit more costly, procedures performed with Medicaid children at a university compared to military dependents at a military base.

Periodontitis in pregnancy: clinical and serum antibody observations from a baboon model of ligature-induced disease.

BACKGROUND: Chronic oral infections that elicit host responses leading to periodontal disease are linked with various sequelae of systemic diseases. This report provides seminal information on the clinical and adaptive immunologic characteristics of a baboon model of ligature-induced periodontitis during pregnancy. METHODS: Female Papio anubis were evaluated for periodontal health at baseline. Ligatures were tied around selected teeth to initiate oral inflammation and periodontitis. Then the animals were bred. At midpregnancy ( approximately 90 days), a clinical evaluation was performed, and additional ligatures were tied on teeth in the contralateral quadrants to maintain progressing periodontitis throughout pregnancy. A final clinical evaluation was done for all experimental teeth after delivery, and ligatures were removed. Serum was collected at all sampling intervals for the determination of antibody levels to a group of 20 oral bacteria. Unligated animals served as controls. RESULTS: At baseline, 16% of animals exhibited minimal plaque and gingival inflammation without periodontal disease. The remaining baboons demonstrated varying levels of inflammation/bleeding, and approximately 20% of the population had periodontal pocketing (>3 mm). Ligated animals expressed increased levels of inflammation and increased probing depths and clinical attachment loss (AL) and could be stratified into multiple subsets postligation based upon changes in clinical parameters at midpregnancy and at delivery. Baboons were categorized into disease susceptibility groups (periodontal disease susceptibility 1 through 4) that described the extent/severity of induced disease during pregnancy. Control animals showed minimal periodontal changes during gestation. Significant differences in serum antibody to multiple oral bacteria were found in animals presenting with periodontitis at baseline and during the 6 months of ligature-induced disease. A significant correlation to antibody to P. gingivalis, which was sustained throughout ligation and pregnancy, was observed with disease presentation. CONCLUSIONS: The clinical presentation at baseline, reflecting the natural history of oral disease in these animals, suggests individual variation that is reflected in the characteristics of the adaptive immune responses to oral bacteria. The variability in the response to ligation with resulting periodontal disease provides a model to document prospectively the relationship between oral and systemic health outcomes.

Role of Aggregatibacter actinomycetemcomitans in glutathione catabolism.

INTRODUCTION: Our previous studies demonstrated that three enzymes, gamma-glutamyltransferase (GGT), cysteinylglycinase (CGase) and cystalysin, are required for the catabolism of glutathione to produce hydrogen sulfide (H(2)S) in Treponema denticola. In this study, we examined glutathione catabolism in Aggregatibacter actinomycetemcomitans. METHODS: The GGT and CGase of A. actinomycetemcomitans were determined by biological methods and GGT was characterized using a molecular biological approach. RESULTS: A. actinomycetemcomitans showed GGT and CGase activity, but could not produce H(2)S from glutathione. The addition of recombinant T. denticola cystalysin, an l-cysteine desulfhydrase, to whole cells of A. actinomycetemcomitans resulted in the production of H(2)S from glutathione. Subsequently, we cloned A. actinomycetemcomitans GGT gene (ggt) and overexpressed the 63 kDa GGT protein. The recombinant A. actinomycetemcomitans GGT was purified and identified. The K(cat)/K(m) of the recombinant GGT from N-gamma-l-glutamyl-4-nitroaniline as substrate was 31/microm/min. The activity of GGT was optimum at pH 6.9-7.1 and enhanced by thiol-containing compounds. CONCLUSION: The results demonstrated that A. actinomycetemcomitans had GGT and CGase activities and that the GGT was characterized. The possible role of A. actinomycetemcomitans in glutathione metabolism and H(2)S production from oral bacteria was discussed.

Periodontal diseases: to protect or not to protect is the question?

For decades, investigations have identified local and systemic humoral immune responses to microorganisms comprising the supra- and subgingival biofilms in the oral cavity. Inflammation and tissue destruction in the periodontium are accompanied by alterations in the quantity, quality, and specificity of antibody. The conundrum in this scenario is the existence of a substantial plasma cell infiltrate at sites of periodontal lesions and a seemingly robust antibody response in the oral cavity and the serum, apparently coincident with progressing disease. Consequently, much effort has been expended to elucidate the critical characteristics of protective humoral responses and to develop strategies for enhancing these unique features. We and others have conducted studies attempting to distinguish disease susceptibility associated with: i) variations in response levels significantly increased to some species with disease, minimal response to others; ii) functional comparisons of antibody subclass differences, genetic regulation, and maturation of responses; iii) microbial and antigenic specificity of the antibody focus on specific pathogens and identification of selected antigens as targets for immunoprotection; and, iv) kinetics of responses during disease and therapeutic interventions linking immune changes with infection and as a measure of treatment success. This report summarizes varied research designs and results, to provide a profile of antibody in health, gingivitis, and periodontitis. These profiles may be used to provide a framework focusing on the humoral response to commensal microorganisms and likely pathogens, as they emerge in the biofilm--etiologic for or in response to disease processes. Models for antibody as a diagnostic adjunct and for predicting protective antibody responses are suggested. These concepts are likely relevant for considering vaccine approaches to periodontitis.

Antigenic specificity of gingival crevicular fluid antibody to Actinobacillus actinomycetemcomitans.

Elevated antibody levels to periodontopathogens in GCF have been identified and used as support for local antibody synthesis in periodontitis. This study examined both cross-sectional and longitudinal GCF samples for the antigenic specificity of antibody in the fluid. GCF samples were collected from each tooth of 27 periodontitis patients infected with A. actinomycetemcomitans. Levels of IgG antibody in the GCF were assessed by means of an ELISA and compared with serum for determination of local elevations. A proportion of those GCF samples that exhibited significantly elevated antibody were examined by Western immunoblotting to outer membrane antigens from A. actinomycetemcomitans. Homologous sera were also examined for comparison of antibody specificities. Of the sites with elevated IgG antibody, 87% were colonized by A. actinomycetemcomitans; however, 46% of sites with A. actinomycetemcomitans infection did not have elevated antibody. Cross-sectional studies identified a 78 to 100% agreement between the antibody specificities in GCF and those in serum. Additionally, patterns of antibody reactivity in both GCF and serum in the subjects were often very distinctive. Longitudinal alterations in GCF antibody were examined in 15 patients through a monitoring interval of up to 2 years and showed a general conservation of specificities. However, 7/15 patients exhibited a definite acquisition of different antibody specificities during the monitoring. These results describe a relationship between elevated local antibody and A. actinomycetemcomitans infection. Furthermore, the antibody specificities in serum appear to reflect generally the local response to this pathogen.

Effects of 0.12% chlorhexidine gluconate on experimental gingivitis in non-human primates: clinical and microbiological alterations.

OBJECTIVE: This study examined the efficacy of 0.12% chlorhexidine gluconate (Peridex) to reduce gingival inflammation in the absence of mechanical hygiene and its effect on the oral microbial ecology in a non-human primate (NhP) model of gingivitis. DESIGN: Twelve NhP were stratified based on existing inflammation into two groups of six NhP per group. Oral hygiene was performed on both groups so as to reach a level of gingival health (BOP < or = 0.3) at the conclusion of the hygiene phase. One group received 30 ml of 0.12% chlorhexidine gluconate twice daily 7 days/week, and a second group received 30 ml of placebo (distilled water colored to match the active) using the same regimen for 10 weeks. MEASUREMENT OUTCOMES: Clinical parameters including plaque (PLI), pocket depth (PD), attachment level (AL), and bleeding on probing (BOP) were evaluated at 2-week intervals. Subgingival plaque samples were collected by paper point at 2-week intervals and cultured for predominant cultivable bacteria. RESULTS: By week 2, there was a difference in BOP between the groups, which reached statistical significance by week 4. This difference in BOP was maintained throughout the course of the study. Chlorhexidine gluconate (0.12%) had no significant effect on PLI, PD, or AL; although PD was greater in the placebo group after week 2 and throughout the study. Microbiologically, at week 4, the treatment group had a reduction in total bacterial counts, as well as Gram positive bacteria, and total black pigmented bacteria, compared to the placebo group. However, only the differences in Actinomyces spp. reached significance. Interestingly, when both groups received only one treatment/day on the weekends (i.e., day 6 and 7), an associated loss of statistically significant differences between the two groups was observed. Additional experiments dosing the non-human primates once daily, 5 days/week yielded no significant differences in clinical parameters, including bleeding, when compared with the placebo group. CONCLUSION: Non-human primates provided a model system of gingivitis for testing antimicrobial agent effects on the subgingival ecology and accompanying inflammatory responses. Chlorhexidine gluconate (0.12%), even in the absence of mechanical hygiene, was effective in inhibiting clinical signs of inflammation, associated with alterations in the subgingival microbial ecology, most notably Actinomyces spp.

Gingival crevicular fluid inflammatory mediators and bacteriology of gingivitis in nonhuman primates related to susceptibility to periodontitis.

The hypothesis to be tested was that the microbiota and resulting local host inflammatory response characteristics in oral conditions of high levels of chronic gingival inflammation increases susceptibility to progressing periodontitis. This study used cynomolgus monkeys, Macaca fascicularis (nonhuman primates), with high and low levels of long-standing gingival inflammation to define the profiles of gingival crevicular fluid mediators, cytokines and immunoglobulins; describe the subgingival microbiota; and evaluate their susceptibility to ligature-induced periodontitis. Sixteen nonhuman primates were stratified into two groups (HI, LO) based upon Bleeding Index as a measure of the natural level of inflammation (HI = 1.26 +/- 0.45; LO = 0.22 +/- 0.16). The host mediator levels, subgingival microbiota, and clinical characteristics of the LO and HI groups were compared after 30 days of oral hygiene, during a 30 day experimental gingivitis (7, 14, and 30 days), and during periodontitis (30, 60, and 90 days). The results demonstrated that nonhuman primates with high levels of long-standing gingival inflammation when compared to those nonhuman primates with low inflammation show: 1) different inflammatory mediator profiles in gingival crevicular fluid (particularly for immunoglobulin A (IgA) and IgG levels), 2) a different quantitative and qualitative subgingival microbiota; and 3) a similar progression of periodontitis. Thus, while variations in host inflammatory responses to local factors exist in the nonhuman primates, an extensive subgingival challenge (such as ligation) may negate these individual differences.

Longitudinal human serum antibody responses to outer membrane antigens of Actinobacillus actinomycetemcomitans.

We hypothesize that serum antibody responses to antigens of a periodontopathogen would vary temporally and that the specificity of these host antibodies would relate to infection and disease activity. To test the hypothesis, we obtained between 6 and 13 serum samples from Actinobacillus actinomycetemcomitans (Aa)-positive (serological and microbiological) periodontitis patients at time points between 18 and 42 months into the study, and evaluated specific antibody responses to outer membrane antigens (OMA) of Aa strain Y4. Sera from these patients detected 22 different OMA. Early-onset (EOP; n=7) and adult (AP; n=11) periodontitis patients responded to 35% and 41% of the OMA, respectively. 2 of 9 sera from healthy subjects detected no antigens and 7/9 sera detected 7% of the OMA (p<0.0001 versus EOP and AP). The frequency of antibody responses to the 17 kDa antigen were similar between diseased, infected patients and the uninfected, normal subjects, suggesting that it may be stimulated as a cross-reactive antigen. Antibody to the 28, 38, and 90 kDa antigens were significantly more common in diseased patients (>90%) versus normal subjects (p<0.01, p<0.002, and p<0.002, respectively) and were unique among diseased, infected patients, which may be indicative of infections with Aa. A 65 kDa antigen showed an increased frequency of reaction in the AP versus the EOP (p=0.01) patients, which exemplified a potential distinction in response to Aa between adult and early-onset disease classifications. Seventeen of 22 OMA could be detected in every sample from at least one patient. Longitudinal samples from seropositive EOP and AP reacted 80-100% of the time with the 17, 28, and 100 kDa antigens. Finally, five antigens of 15, 38, 58, 65, and 79 kDa were detected in 33-83% of the seropositive patients; however, antibody to these OMA reacted variably at different sampling points, suggesting some antigenic response diversity over time.

Systemic manifestations of periodontitis in the non-human primate.

This report describes our findings regarding the potential contribution of periodontitis to atherosclerotic processes using a nonhuman primate model. The goal of the investigations was to target general mechanisms which could describe the association of these disease processes, including: (i) systemic translocation of bacteria/products during periodontitis; (ii) alterations in systemic inflammatory biomarkers during periodontitis; and (iii) the relationship of periodontitis to serum lipids/lipoproteins. Increases in serum endotoxin (e.g. LPS) during ligature-induced periodontitis were observed in these animals. We determined serum levels of various acute phase reactants and chemokines (e.g. CRP, alpha 1-antitrypsin, haptoglobin, fibrinogen, IL-8). A number of these host factors were significantly increased during gingivitis and/or periodontitis. Finally, we observed specific changes in serum lipid levels (cholesterol, triglycerides, HDL, LDL) and lipoproteins (apoA-I) during periodontitis, which were exacerbated by exposure of the animals to a diet with elevated fat content. Thus, we have described systemic manifestations of periodontitis that include detection of bacterial products, inflammatory biomarkers, and dyslipoproteinemia consistent with an increased atherogenic risk.

Immunization with Porphyromonas gingivalis cysteine protease: effects on experimental gingivitis and ligature-induced periodontitis in Macaca fascicularis.

Targeting bacterial virulence factors such as proteases for immunization may hold the key to limiting or preventing loss of attachment and alveolar bone in periodontal disease. This study examined the clinical, microbiological, and immununological responses following active immunization with a purified Porphyromonas gingivalis cysteine protease (porphypain-2) in the nonhuman primate (Nhp) Macaca fascicularis. One group of Nhp was immunized with porphypain-2 antigen while control Nhp received placebo injections. All Nhp were subjected to experimental gingivitis followed by ligature-induced periodontitis in a split-mouth design. An enzyme-linked immunosorbent assay demonstrated that immunization elicited a significantly elevated and specific IgG antibody response to both whole cell P. gingivalis (36-fold) and to porphypain-2 (194-fold). Checkerboard hybridization DNA analysis of subgingival plaque from ligated sextants demonstrated that 25% more Gram-negative anaerobic species became significantly elevated from baseline and at earlier timepoints in the control group than in the immununized group. Immunization with this protease did not suppress the emergence of P. gingivalis. Clinical indices showed few changes related to immunization. Alveolar bone density changes demonstrated a highly significant loss in ligated sextants compared to non-ligated sextants within the control group (P < 0.001), and a smaller but significant difference within the immunized group (P = 0.043). Comparison of ligated sextants only demonstrated more bone loss in the control group versus the immunized group (-13.07+/-9.51 versus -9.41+/-6.18; computer-assisted densitometric image analysis units +/- SD); the difference approached, but did not reach, significance. The results suggest that porphypain-2 may contribute to the pathogenic potential of the subgingival plaque microbiota in the Nhp model of ligature-induced periodontitis, and that active immunization with porphypain-2 appeared capable of altering this pathogenic response.

Host response assessment in recurring periodontitis.

Data derived from periodontitis patients have provided support for a relationship between the distribution of selected members of the periodontopathic microbiota and antibody levels to the intact bacteria in both serum and GCF. These data are consistent with the systemic antibody as a reflection of the host response to an infectious process associated with an episode of disease activity. The purpose of this report is to address the concept that the host antibody responses may help to elucidate the specific etiologic agents and be used to model the risk for future periodontal disease progression in recurring periodontitis. These findings from one study in adult periodontitis patients indicated that elevations in certain antibody specificities are most closely associated with patients exhibiting a risk of disease recurrence. Furthermore, analysis of the frequency of antibody elevations suggested that patients capable of maintaining elevated antibody to these pathogens post-treatment, may be indicative of an individual at less risk. A 2nd investigation was implemented to address questions concerning host-parasite interactions in A. actinomycetemcomitans-associated recurring periodontitis. The results showed distinctive characteristics of local and systemic antibody responses and A. actinomycetemcomitans infection in patients with varying extents of recurrent disease. These longitudinal studies developed evidence for the potential of local and/or systemic antibody responses as indicators of periodontal disease recurrence.

Antigen specificity of serum antibody in A. actinomycetemcomitans-infected periodontitis patients.

We hypothesized that serum antibody with selected antigen specificities would relate to infection and disease in the patients and, thus, describe the characteristics of potential protective antibody. This study used serum samples from 24 periodontitis patients with subgingival infection and elevated serum IgG antibody to A. actinomycetemcomitans to define the antigenic specificities of IgG, IgM, IgA, and IgG1-4 antibody to A. actinomycetemcomitans strain Y4 outer membrane antigens (OMA). Uniform IgG antibody (> 70% of the patients) was noted to antigens with M(r) of 65, 38, 29, and 17 kDa. Both IgA and IgM specificities reflected those shown for IgG in each patient. IgG1 and IgG2 antibody reacted with several OMA bands in each patient, while IgG3 antibodies were directed to numerous OMA bands in many patients and represented the most broad-based response. The IgG4 response patterns were limited to a few OMA bands. We noted a prominent occurrence of IgG reactions with OMA bands that were characteristic for individual patients. The frequency of responses to OMA of higher M(r) (i.e., > 80 kDa) and to the 34-, 31-, and 24-kDa antigens was positively related to the total IgG antibody levels. Antibody reactive with OMA bands at 65-, 38-, 29-, 17-, 15-, and 11-kDa antigens was detected in patients with few to many teeth infected with A. actinomycetemcomitans. Furthermore, patients with a high percentage of teeth with > or = 6 mm pockets had a decreased frequency of responses to the high-M(r) antigens (i.e. > 90 kDa) as well as to the 58-kDa antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Gingival crevicular fluid antibody to Actinobacillus actinomycetemcomitans in periodontal disease.

We identified antibody isotypes and subclass proportions in gingival crevicular fluid to understand the potential protective ability of these antibodies towards infection with Actinobacillus actinomycetemcomitans. Immunoglobulin G (IgG) 1-4 antibody levels to A. actinomycetemcomitans serotype b were quantified in serum and gingival crevicular fluid from 20 periodontitis patients who had at least one subgingival plaque sample with cultivable A. actinomycetemcomitans. The subclass antibody levels in the patients' sera were IgG1 = IgG2 > IgG3 > IgG4. A portion of the gingival crevicular fluid samples had IgG (15.7%; range: 0-52%) and IgA (2.5%; range: 0-15%) antibody that was significantly elevated compared with serum. Gingival crevicular fluid samples with elevated IgG antibody were analyzed for the subclass distribution and showed elevated IgG3 (58%), IgG4 (35%), IgG1 (25%) and IgG2 (25%) antibody in the gingival crevicular fluid. These results demonstrated a characteristic distribution of both serum and gingival crevicular fluid IgG subclass responses to A. actinomycetemcomitans. We also examined the sites with elevated antibody in each subclass for the presence of A. actinomycetemcomitans in the subgingival microbiota. The results showed that > 95% of sites with elevated IgG4 were colonized, whereas < 50% of sites with elevated IgG2 demonstrated this microorganism. IgG2 and IgG4 levels were primarily elevated in diseased sites, whereas IgG4 elevations were absent in healthy sites. The frequency and distribution of antibody in the gingival crevicular fluid as related to colonization with this microorganism were consistent with localized host-parasite interactions at individual tooth sites. The relative subclass distribution of elevated gingival crevicular fluid antibody was shown to be IgG3 > IgG4 > IgG2 = IgG1. These antibody types suggest that the potential exists for this local antibody to A. actinomycetemcomitans to play an important role in the gingival sulcus in relationship to colonization and clinical presentation.

Early-onset periodontitis in Hispanic-American adolescents associated with A. actinomycetemcomitans.

This study examines the frequency of oral disease in an adolescent population, and assesses the relationship to Actinobacillus actinomycetemcomitans. A total of 470 eighth grade students from San Antonio, Texas, were examined clinically for number of teeth, frequency of gingival inflammation, frequency of sites with BOP, and frequency of sites with 3-5 mm pockets, and pockets > 5 mm. The population ranged in age from 12 to 17 yr and was 93% Hispanic. Heavy accumulations of plaque and calculus were frequently observed and were associated with gingival inflammation, as 95.6% of the students exhibited bleeding on probing, and 99.6% of the students presented with at least on quadrant of inflammation upon visual examination. Significantly, 25.7% of the students exhibited early-onset periodontitis (EOP) with 1.7% diagnosed as LJP. Many students exhibited substantial levels of plaque and calculus, but no clinical evidence of loss of attachment. Subjects with periodontitis (EOP or LJP) presented with elevated systemic IgG antibody to A. actinomycetemcomitans serotype b and subgingival plaque samples positive for the microorganism. These results describe the prevalence of EOP/LJP in an adolescent Hispanic population from South Texas. The findings support that A. actinomycetemcomitans may represent a pathogen in periodontitis and while oral health care may be poor, contact with the microorganism appears to be required to initiate disease in this population.

Subgingival distribution of A. actinomycetemcomitans in periodontitis.

This investigation developed an experimental design that (1) detailed the distribution of A. actinomycetemcomitans in subgingival plaque related to the level of serum antibody to this pathogen; (2) used broad based subgingival plaque sampling to allow a definition of the distribution of A. actinomycetemcomitans infection in periodontitis patients; (3) described the distribution of A. actinomycetemcomitans serotypes in patients and within sites; and, (4) assessed how this infection impacted upon local clinical symptoms of disease. We noted a significant positive relationship between the level of IgG anti-A. actinomycetemcomitans antibody and the frequency of teeth infected until nearly 13 teeth demonstrated an infection. Furthermore, the results showed a generally negative relationship between the antibody level and the burden of A. actinomycetemcomitans in the infected sites. Interproximal sites associated with first molar teeth were the predominant sites for subgingival colonization; incisors were also frequently infected in this population. The first molar teeth also exhibited the greatest level of A. actinomycetemcomitans, while the incisors demonstrated a high level of A. actinomycetemcomitans in individual sites. The results clearly indicated the majority of the sites sampled were colonized by a single serotype of A. actinomycetemcomitans. We detected A. actinomycetemcomitans nearly 2 x times more frequently and a significant increase in the proportion of A. actinomycetemcomitans was found in samples obtained from teeth with bleeding on probing. The results also showed a significant trend for both pocket depth and attachment levels to be related to the presence and proportion of A. actinomycetemcomitans in the subgingival plaque. These findings detail the microbiological, immunological and clinical characteristics of a unique subset of periodontitis patients that appear to exhibit disease associated (caused?) with A. actinomycetemcomitans infection irrespective of clinical categorization. The results support a unique distribution of this microorganism in the subgingival ecology that is related to active host immune responses and clinical presentation of the tooth.

Characteristics and utilization of antibody measurements in clinical studies of periodontal disease.

The detection and quantitation of immune responses to infections have long been used as a diagnostic tool in medical infections. Recently, increasing evidence has supported that active, specific antibody responses to selected members of the subgingival microbiota are noted in periodontitis patients. This report describes the various specificities of this antibody as they relate to periodontitis classification and prognosis. The functional aspects of the serum antibody have come under increasing scrutiny to understand better the potential immunologic mechanisms acting in the periodontium. Data are available that describe opsonizing potential, complement fixing ability, blocking functions, and anti-toxic capacity for the antibody. Longitudinal alterations in specific antibody levels are shown to relate to infection and accompany changes in the burden of a specific microorganism in the subgingival plaque. Thus, these antibody changes could be useful indicators of altered host-parasite interactions that presage a disease-active episode. Finally, studies were designed to examine the ability of antibody to reflect the effects of treatment on the disease. The results indicated that specific antibody levels change with mechanical, antimicrobial, and anti-inflammatory treatments. The findings described in this report suggest that evaluation of the level and specificity of serum antibody can be a beneficial adjunct in designing and implementing clinical studies delineating the initiation, progression, and treatment of periodontitis.

Serum antibody in Actinobacillus actinomycetemcomitans-infected patients with periodontal disease.

This study was designed to (i) delineate the characteristics of serum antibody responses to Actinobacillus actinomycetemcomitans in patients with periodontitis who are infected with A. actinomycetemcomitans; irrespective of disease classification; (ii) assess the relationship of the elevated antibody levels to colonization of the oral cavity by A. actinomycetemcomitans; and (iii) describe the serotype distribution of A. actinomycetemcomitans and antibodies to the microorganism in infected patients with various clinical classifications. To compare the levels of various isotype-specific antibodies to the different antigens, studies were performed that allowed quantitation of each isotype-specific antibody in a human reference standard. By using this reference standard, it was shown that the levels of immunoglobulin G (IgG), IgM, and IgA responses to A. actinomycetemcomitans were similar among the infected patients, irrespective of disease classification. Also, we demonstrated that the serum antibody response to serotype b was quantitatively greater in all isotypes. Our findings indicate that b was the most frequent A. actinomycetemcomitans serotype detected in the patients and appears to be capable of initiating a substantial serum IgG antibody response that may contain cross-reactive antibodies to other serotypes of A. actinomycetemcomitans. Generally, in cases in which the response to a single serotype was elevated, only that type of A. actinomycetemcomitans was detected in the plaque. Individuals exhibiting elevated antibodies to multiple serotypes were most consistently colonized by the serotype b microorganism. This study represents the first report detailing the distribution of IgG subclass antibodies to A. actinomycetemcomitans in periodontal disease. The results demonstrated that the primary responses of patients with periodontitis to A. actinomycetemcomitans were of the IgG1 and IgG3 subclasses, which is consistent with elicited responses to protein antigens. In contrast, the primary subclass response in normal subjects was limited to the IgG2 subclass and may represent broader cross-reactivity to polysaccharide antigens-lipopolysaccharide from the bacteria.