Host Response In Periodontitis Research Articles

Liquid chromatography method with tandem mass spectrometry and fluorescence detection for determination of inflammatory biomarkers in gingival crevicular fluid as a tool for diagnosis of periodontal disease

The new ultra-high performance liquid chromatography method with tandem mass spectrometry and fluorescence detection allowing fast, selective, and high-throughput analysis of neopterin, kynurenine, tryptophan, and creatinine in gingival crevicular fluid (GCF) has been optimized. Defining the pathophysiology of periodontal disease and identification of potential diagnostic test for active periodontitis remains a significant challenge in the field of oral disease diagnosis. Analysis of GCF provides a non-invasive means of evaluating the role of the host response in periodontal disease. In addition, the analysis of GCF provides an information about current inflammation level of sampled site/tooth. Determination of GCF inflammatory biomarkers such as neopterin, kynurenine, and tryptophan can contribute to diagnosis, evaluation of treatment, and progression of periodontal diseases such as gingivitis and periodontitis. The separation of target analytes was carried out using a column Kinetex™ Polar C18 100 Å, (100 × 3.0 mm) packed with 2.6 µm core-shell particles applying an elution with a gradient formed from 0.2% aqueous formic acid and 90% aqueous acetonitrile. Kynurenine, tryptophan, and creatinine were detected using mass spectrometry with electrospray ionization to improve the sensitivity while neopterin was detected using fluorescence detection. The separation of these four substances was achieved after using a very simple sample preparation technique convenient for small amount of biological sample. Only less than 20 µL sample was needed and the separation was completed in 4 min. MS/MS analysis was performed using multiple reaction monitoring (MRM) under a positive ionization mode. Deuterium labeled internal standard was used for the more precise quantification. The lower limits of quantification (LLOQ) for target analytes were 0.50 × 10–3 µmol/L for neopterin, 0.10 µmol/L for kynurenine, and 0.20 µmol/L for tryptophan and creatinine. The within-run and between-run accuracy were in a range of 96.67–114.77% for all quality controls and LLOQ of all analytes. Matrix effect, extraction recovery, and stability testing have all been investigated. The method was tested with real-life samples using GCF collected from patients suffering from periodontitis and from healthy controls. Neopterin levels in patients were significantly higher (P = 0.020) than in healthy subjects and indicate good potential of this method for using in evaluation of periodontal pathogenesis and healing outcomes following a treatment.

Novel synthetic peptide derived from Porphyromonas gingivalis Lys-gingipain detects IgG-mediated host response in periodontitis

Porphyromonas gingivalis is a keystone pathogen in periodontitis. Analysis of the immunogenicity of its virulence factors may provide insight into the host response to this infection. The Kgp12 (IEDB Epitope ID 763561), an epitope of Lys-gingipain (Kgp) virulence factor from P. gingivalis ATCC 33277, elicits an immunoglobulin G (IgG) immunoreactivity with low cross-reactivity and, therefore, more specificity. The aim of the present study was to determine in silico the localization of Kgp12 within the protein and to evaluate the IgG host response to this novel Kgp peptide through its capacity to differentiate individuals with different periodontal status. Sera of 71 volunteers were tested by indirect ELISA to detect the IgG immunoreactivity specific to Kgp12, as well as to the protein HmuY and to the sonicated total extract of P. gingivalis ATCC33277, both used as gold standard. The participants had no systemic disease and were classified according to periodontal clinical parameters to comparison, firstly, into periodontitis (P) and without periodontitis (WP) groups and, secondly, into periodontitis (P), gingivitis (G) and clinically health (CH) ones. All the antigens tested, Kgp12 (p = 0.02), HmuY (p = 0.00) and P. gingivalis extract (p = 0.03), could differentiate P from WP groups considering IgG serum levels. P group also had higher IgG levels specific to Kgp12 (p = 0.03), HmuY (p < 0.01) and P. gingivalis extract (p = 0.01) when compared to G group. We conclude that the Kgp12 synthetic peptide was useful to detect the IgG-mediated host response signaling that it is a promising epitope to analyze the immunogenicity of P. gingivalis.

Cytokines and MMPs levels in gingival crevicular fluid from patients with chronic periodontitis before and after non-surgical periodontal therapy

The study of host response in periodontal disease may provide a mechanism to monitor disease progression. The purpose of the present research was to determine the levels of IL-1α, IL-1β, TNF-α, IL-6, IL-6sR, IL-8, IL-10, MMP-3 and MMP-8 in gingival crevicular fluid (GCF), before and after non-surgical periodontal treatment (NSPT) in order to evaluate therapy response. Methodology: Eleven patients diagnosed with chronic periodontitis and eleven healthy subjects were selected for this study. Clinical measurements, including probing depth (PD) and clinical attachment loss (CAL) were carried out in patients diagnosed with chronic periodontitis and periodontal healthy controls. The clinical indexes evaluated were: gingival index (GI) and plaque index (PI). Samples of GCF were taken from one tooth per quadrant before and 45 days after NSPT. The levels of inflammatory mediators were measured by ELISA. Results: The values of all clinical parameters decreased significantly after treatment. The concentration levels of all cytokines and MMP-3 and MMP-8 in the GCF sample were higher in patients diagnosed with chronic periodontitis compared to the healthy group. All inflammatory mediators decreased after therapy, but did not reach control values; IL-6, Il-6sR, IL-10 and TNF-α, attained the highest reduction (70% -54%); the vales of MMP3, IL-1α, IL-1β and IL-8 were reduced between 50% - 34%; and MMP-8 showed the lowest decrease (28%). Conclusion: All clinical parameters and cytokines levels decreased after NSPT. The mediators TNF-α IL-6, IL-6sR, and IL-10 showed the largest variation between before and after NSPT and could thus be used to evaluate therapy response.

Revisiting the Page & Schroeder model: the good, the bad and the unknowns in the periodontal host response 40years later.

In their classic 1976 paper, Page & Schroeder described the histopathologic events and the types of myeloid cells and lymphocytes involved in the initiation and progression of inflammatory periodontal disease. The staging of periodontal disease pathogenesis as 'initial', 'early', 'established' and 'advanced' lesions productively guided subsequent research in the field and remains fundamentally valid. However, major advances regarding the cellular and molecular mechanisms underlying the induction, regulation and effector functions of immune and inflammatory responses necessitate a reassessment of their work and its integration with emerging new concepts. We now know that each type of leukocyte is actually represented by functionally distinct subsets with different, or even conflicting, roles in immunity and inflammation. Unexpectedly, neutrophils, traditionally regarded as merely antimicrobial effectors in acute conditions and protagonists of the 'initial' lesion, are currently appreciated for their functional versatility and critical roles in chronic inflammation. Moreover, an entirely new field of study, osteoimmunology, has emerged and sheds light on the impact of immunoinflammatory events on the skeletal system. These developments and the molecular dissection of crosstalk interactions between innate and adaptive leukocytes, as well as between the immune system and local homeostatic mechanisms, offer a more nuanced understanding of the host response in periodontitis, with profound implications for treatment. At the same time, deeper insights have generated new questions, many of which remain unanswered. In this review, 40years after Page & Schroeder proposed their model, we summarize enduring and emerging advances in periodontal disease pathogenesis.

The effect of an inhibitor of gut serotonin (LP533401) during the induction of periodontal disease.

LP533401 is an inhibitor of tryptophan hydroxylase 1, which regulates serotonin production in the gut. Previous work indicates that LP533401 has an anabolic effect in bone. Thus, we hypothesized that inhibition of gut serotonin production may modulate the host response in periodontal disease. In this study, we aimed to analyze the effects of LP533401 in a rat periodontitis model to evaluate the role of gut serotonin in periodontitis pathophysiology. Twenty-four rats were divided into three groups: treated group (T: ligature-induced periodontal disease and LP533401, 25mg/kg/d) by gavage; ligature group (L: ligature-induced periodontal disease only); and control group (C: without ligature-induced periodontal disease). After 28d, radiographic alveolar bone support was measured on digital radiographs, and alveolar bone volume fraction, tissue mineral density and trabeculae characteristics were quantified by microcomputed tomography in the right hemi-mandible. Left hemi-mandibles were decalcified and alveolar bone loss, attachment loss and area of collagen in the gingiva were histologically analyzed. Significant difference between the L and C groups was found, confirming that periodontal disease was induced. We observed no difference between the T and L groups regarding alveolar bone destruction and area of collagen. LP533401 (25mg/kg/d) for 28d does not prevent bone loss and does not modulate host response in a rat model of induced periodontal disease.

Estimation of salivary neopterin in chronic periodontitis.

Periodontal diseases are the most common bacterial infection predominantly associated with Gram-negative microorganisms that exist in the subgingival biofilm. Analysis of saliva provides a noninvasive means of evaluating the role of the host response in periodontal disease. Though salivary enzymes can be used as the biomarkers, neopterin has been recently used as one of the important diagnostic tools in the field of periodontics. Hence, we aimed to identify the neopterin levels in unsimulated saliva from the chronic periodontitis patients and compare them with the periodontally healthy subjects. Twenty subjects participated in the study and were categorized as the experimental group (chronic periodontitis patients) and control groups (healthy subjects). Unstimulated saliva samples were collected from both the groups for neopterin estimation. Neopterin in saliva was estimated using Shimadzu High Performance Liquid Chromatography with LC-20AD pump system, equipped with RF-10 AXL fluorescence detector. Data were expressed as mean±SD and analyzed using GraphPad Prism version 6.0 (California, USA). Statistical analysis was done by Student's t-test. The neopterin level in unstimulated saliva was found to be higher in the experimental group than the control group with P≤0.05. The chronic periodontitis patients showed higher neopterin level in unstimulated saliva as compared to control. Hence, neopterin can be used as a potential biomarker for identification of the periodontal disease in its initial stage can help in preventing the disease progression.

Inflammatory and immune pathways in the pathogenesis of periodontal disease

The pathogenesis of periodontitis involves a complex immune/inflammatory cascade that is initiated by the bacteria of the oral biofilm that forms naturally on the teeth. The susceptibility to periodontitis appears to be determined by the host response; specifically, the magnitude of the inflammatory response and the differential activation of immune pathways. The purpose of this review was to delineate our current knowledge of the host response in periodontitis. The role of innate immunity, the failure of acute inflammation to resolve (thus becoming chronic), the cytokine pathways that regulate the activation of acquired immunity and the cells and products of the immune system are considered. New information relating to regulation of both inflammation and the immune response will be reviewed in the context of susceptibility to, and perhaps control of, periodontitis.

Protective effects of ginkgo biloba extract on ligature-induced periodontitis in rats

Objective. The aim of this study was to test the hypothesis that the systemic administration of extract of Ginkgo biloba (EGb) would prevent excessive tissue destruction in ligature-induced periodontitis in a rat model. Materials and methods. Thirty-two male Wistar albino rats were used in the current study. The rats were randomly divided into four groups of eight rats each: (1) non-ligated treatment (NL) group, (2) ligature-only (LO) group, (3) ligature plus GB28 (28 mg/kg, daily for 11 days) group and (4) ligature plus GB56 (56 mg/kg, daily for 11 days) group. Results. Measurement of alveolar bone loss in the mandibular molar tooth revealed significantly lower bone loss values in the LO group compared to groups NL, GB28 and GB56 (p < 0.05). Conclusion. The present results are the first data which suggests that host response in periodontitis can be modified by EGb administration. EGb minimized progression of periodontal disease.

Association between genetic risk score and periodontitis onset and progression: A pilot study

AimRecent research has focused attention on the single nucleotide polymorphisms (SNPs) involved in the host response in periodontitis. However, so as to combine the relatively small effects of individual genes the use of multi locus genetic risk (GRS) has been proposed. This study aims to evaluate whether the genetic risk score may predict periodontitis onset and progression. Materials and methodsFifty patients were divided into various groups according to periodontal status. Total DNA was isolated from epithelial oral cells by a masked operator and the selected SNPs were analysed. A GRS was calculated using an additive model. ResultsWe found a strong association only between TNF rs1800629 and diffused forms of periodontitis. Data show that GRS is able to discriminate diffused forms of periodontitis from localized ones. Finally, a progressive increase of the GRS is evident in advanced periodontitis in comparison with early forms. DiscussionIn recent years, research on genetic polymorphism has had limited success in predicting the susceptibility to periodontal disease. However, our results indicate that the use of the genetic risk score could be promising. Further studies are necessary to include data from multiple genes so as to confirm our result.

Oral Pathogens, Immunity, and Periodontal Diseases

The pathogenesis of periodontal disease is not fully understood. Subgingival bacterial pathogens are essential for the initiation and development of the disease, but it is the resulting host reaction that primarily mediates tissue damage. Complex inflammatory and immune responses are involved in the progression of periodontitis. Activated monocytes, macrophages, and fibroblasts all produce cytokines that orchestrate the cascade of destructive events in periodontal tissues. Cells from individuals with immune-mediated diseases exhibit different cytokine profiles, which may be due to genetic differences among individuals, causing hyper-responsiveness in some patients. Adaptive immunity, involving Bcells and subsets (B1, B2), plasma cells, and T-cell subsets, can be estimated by their cytokine profiles (Th1, Th2, Th17). Based on these data, it may be feasible to distinguish a protective from a destructive host response in periodontitis. Gene polymorphisms of inflammatory markers are also associated with the presence of viable periodontopathogenic bacteria. Lipopolysaccharides of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans are considered key factors in the development of chronic periodontitis. Lipopolysaccharides utilize toll-like receptor-2 and increase osteoblastic expression of RANKL, interleukin-1, interleukin-8, prostaglandin E2, and tumor necrosis factor-α, which are all known to induce osteoclastic activity. The aforementioned findings support the hypothesis that complex interactions among microbiota, immune system, and host genome may underlie susceptibility to aggressive periodontitis. This article reviews research on periodontopathogens and provides an update on immunity paradigms in the pathogenesis of periodontal diseases. Keywords: Periodontitis, immunity, periodontopathogen, Pathogens, Periodontal Diseases, macrophages, fibroblasts, cytokines, monocytes, B-cells, plasma cells, T-cell, Adaptive immunity, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Lipopolysaccharides, toll-like receptor-2, interleukin-1, interleukin-8, prostaglandin E2, tumor necrosis factor-, gingivitis, diabetes, matrix metalloproteinases, arachidonic acid, lipoxins, Osteoprotegerin, osteoimmunology, homeostasis, Langerhans cells, lamina propria, immunoglobulin, Tannerella forsythensis, Staphylococus aureus, pathogen-associated molecular patterns, CD207, Porphyiromona gingivalis, Tannerella forsytensis, Treponema dentícola, reverse-transcription PCR, RT-PCR

Evaluation of Gingival Crevicular Fluid Adrenomedullin and Human Neutrophil Peptide 1–3 Levels of Patients With Different Periodontal Diseases

Antimicrobial peptides participating in the innate host response are important contributors for maintaining the balance between health and disease. The aim of the present study is to investigate the levels of gingival crevicular fluid (GCF) adrenomedullin and human neutrophil peptides 1 through 3 (HNP1-3) in patients with different periodontal diseases. A total of 77 subjects, including 20 patients with chronic periodontitis, 18 patients with generalized aggressive periodontitis, 20 patients with gingivitis, and 19 healthy subjects, were included in the present study. The probing depth, clinical attachment level, plaque index, and papilla bleeding index were assessed in all study subjects. GCF samples were analyzed for evaluating adrenomedullin and HNP1-3 levels by enzyme-linked immunosorbent assay. The present study demonstrated that the periodontitis groups had a significantly higher total amount of GCF adrenomedullin compared to the gingivitis and healthy control groups after adjusting for age and gender (P <0.05). Additionally, GCF adrenomedullin levels were positively correlated with clinical periodontal parameters of sampling sites (P <0.05). The total amount of GCF HNP1-3 was not different among the study groups, and there was no correlation between the total amount of GCF HNP1-3 and clinical periodontal parameters (P >0.05). Our results suggest a defensive role for adrenomedullin during the host response in periodontal disease. Additionally, the lack of the HNP1-3 antimicrobial peptide might point to the deficiency of one of the protective mechanisms for periodontal tissues.

Gingival crevicular fluid in the diagnosis of periodontal and systemic diseases

Gingival crevicular fluid (GCF) can be found in the physiologic space (gingival sulcus), as well as in the pathological space (gingival pocket or periodontal pocket) between the gums and teeth. In the first case it is a transudate, in the second an exudate. The constituents of GCF originate from serum, gingival tissues, and from both bacterial and host response cells present in the aforementioned spaces and the surrounding tissues. The collection and analysis of GCF are the noninvasive methods for the evaluation of host response in periodontal disease. These analyses mainly focus on inflammatory markers, such as prostaglandin E2, neutrophil elastase and beta-glucuronidase, and on the marker of cellular necrosis-aspartat aminotransferase. Further, the analysis of inflammatory markers in the GCF may assist in defining how certain systemic diseases (e.g., diabetes mellitus) can modify periodontal disease, and how peridontal disease can influence certain systemic disorders (atherosclerosis, preterm delivery, diabetes mellitus and some chronic respiratory diseases). Major factors which influence the results obtained from the analyses of GCF are not only the methods of these analyses, but the method of GCF collection as well. As saliva collection is less technique-sensitive than GCF collection, some constituents of saliva which originate from the GCF can be analysed as more amenable to chairside utilization.

Host responses in periodontal diseases: a preview

Host responses in periodontal diseases: a preview

Aspects of adaptive host response in periodontitis

To review host response in periodontitis with respect to cellular composition of lesions, T cell receptor (TCR) gene expression, cytokine profiles of T-helper (Th) cells and autoimmune components. The studies included were confined to human material (biopsies, gingival crevicular fluid, blood from subjects with periodontitis). In periodontitis lesions, plasma cells are the most common cell type and represent about 50% of all cells, while B cells comprise about 18%. The proportion of B cells is larger than that of T cells and Th cells occur in larger numbers than T cytotoxic cells. Polymorphonuclear cells and macrophages are found in fractions of less than 5% of all cells. Lesions in aggressive and chronic forms of periodontitis exhibit similar cellular composition. Differences in disease severity, however, may reflect increases in plasma cell and B cell densities. B cells serve as important antigen-presenting cells in periodontitis. The periodontitis lesion expresses a unique TCR gene repertoire that is different from that in blood. The role of superantigens in periodontitis is unclear. There are few studies using comparative designs and unbiased quantitative methods regarding Th-1 and Th-2 cells in periodontitis. The relative dominance of B cells and plasma cells in periodontitis lesions cannot entirely be explained by enhanced Th-2 functions but maybe because of an imbalance between Th-1 and Th-2. Autoimmune reactions are evident in periodontitis lesions. The role of auto-antibodies in the regulation of host response in periodontitis, however, needs to be clarified. Auto-reactive B cells occur in larger proportions in subjects with periodontitis than in healthy controls.

Proteinase-activated Receptor-2 (PAR2) Agonist Causes Periodontitis in Rats

Proteinase-activated receptor-2 (PAR2) is a G-protein-coupled receptor that mediates cellular responses to extracellular proteinases. Since PAR2 is expressed by oral epithelial cells, osteoblasts, and gingival fibroblasts, where its activation releases interleukin-8, we hypothesized that PAR2 activation may participate in periodontal disease in vivo. We investigated the role of PAR2 activation in periodontal disease in rats. Radiographic and enzymatic (myeloperoxidase) analysis revealed that topical application of PAR2 agonist causes periodontitis but also exacerbates existing periodontitis, leading to significant alveolar bone loss and gingival granulocyte infiltration. Inhibition of matrix metalloproteinase (MMP) and cyclo-oxygenase (COX) decreased PAR2 agonist-induced periodontitis. More specifically, the overexpression of COX-1, COX-2, MMP-2, and MMP-9 in gingival tissues suggests that they are involved in PAR2-induced periodontitis. In conclusion, PAR2 agonist causes periodontitis in rats through a mechanism involving prostaglandin release and MMP activation. Inhibition of PAR2 may represent a novel approach to modulate host response in periodontitis.

Plasma antibody levels in periodontitis patients and controls

A major aspect of the adaptive host response in periodontitis is the production of antibodies. Several risk and susceptibility factors for periodontitis, including smoking, age and composition of the subgingival microflora, have also been suggested to influence antibody production. The present study was conducted to investigate plasma levels of immunoglobulin (Ig) G, A and M antibodies in periodontitis patients of Caucasian European heritage in relation to disease severity, smoking, diagnosis and prevalence of periodontopathogens. In this study, 29 patients with severe periodontitis, 51 with moderate periodontitis and 55 controls without periodontal destruction were enrolled. From the total of 80 patients, 18 were diagnosed with aggressive periodontitis and 62 with chronic periodontitis. Total IgG, IgA and IgM as well as IgG isotypes were analyzed in plasma samples. Levels of total IgG, IgA and IgM were not different between patients and controls; however, in periodontitis, higher levels of IgG1 and IgG2 were observed. Smoking appeared to be significantly and inversely related to antibody levels in periodontitis, in particular for total IgG and IgG2. The absence of an elevated total IgG and IgG2 in smoking patients was irrespective of severity, prevalence of periodontal pathogens and diagnosis. The elevation of total IgG and IgG1 and IgG2 in non-smoker periodontitis patients was observed in patients with moderate periodontitis and even greater in patients with severe periodontitis, but was independent whether patients were infected with Actinobacillus actinomycetemcomitans or Porphyromonas gingivalis and independent of diagnosis. Clinically, it was observed that patients who smoked had more periodontal bone loss; the current findings on antibody levels may be one of several mechanisms related to more extensive periodontal breakdown in smoker patients. The current study shows that non-smoker periodontitis patients have higher levels of total IgG and IgG2 than smoker periodontitis patients.

Neopterin Profile to Evaluate the Effectiveness of Treatment in Aggressive Periodontitis

Abstract Periodontal disease results from the interaction of the host defence mechanisms with the microbial dental plaque. Analysis of gingival crevicular Huid (GCF) provides a non-invasive means of evaluating the role of the host response in periodontal disease. Based on our previous study, demonstrating increased levels of neopterin in GCF and saliva from patients with aggressive periodontitis (AgP), the aim of this study was to evaluate the effect of periodontal treatment on the levels of neopterin in GCF, saliva and urine of patients with AgP. Pre-treatment values of neopterin in GCF were 4.04 ± 0.86 nmol/ml for the AgP group (n=8) and 2.68 ± 0.90 nmol/ml fyr the control group (n=8; difference not significant). After periodontal treatment, the level of ncoptei in was found 2.38 ± 0.72 nmol/ml in the patient group which did not differ f r om pre-treatment levels. The salivary neopterin concentration was higher in both AgP groups (14.14 ± 2.85 nmol/1 and 8.02 ± 3.12 nmol/1, before and after periodontal treatment) than in controls (2.58 ± 0.3 nmol/1; both p&lt;0.05). No significant difference in salivary neopterin level was observed in patients before and after periodontal treatment. Concentrations of urine neopterin in patients before treatment were 188.5 ± 30.98 μηιοί neopterin/mol creatinine and 168.1 + 20.21 μηιοί in controls (difference not significant). Following periodontal treatment, the urinary neopterin levels (310.1 ± 39.82 μηιοί neopterin/mol creatinine) were higher when compared to the baseline levels and to controls (p&lt;0.05). Our results suggest that neopterin in saliva and GCF might be associated with the periodontal diseases process.

Gingival crevicular fluid a marker of the periodontal disease activity

Gingival crevicular fluid (GCF) is an inflammatory exudate that can be collected at the gingival margin or within the gingival crevice. The biochemical analysis of the fluid offers a non invasive means of assessing the host response in periodontal disease. Active phase of periodontal disease process can be measured or assessed by the constituents of gingival fluid. Bacterial enzymes, bacterial degradation products, connective tissue degradation products, host mediated enzymes, inflammatory mediators, extracellular matrix proteins either together or individually can be detected in higher levels in gingival crevicular fluid during active phase of periodontitis.

Interactions between non-immune host cells and the immune system during periodontal disease: role of the gingival keratinocyte.

Periodontal disease and inflammatory dermatoses, such as psoriasis, are characterized by the accumulation of dense inflammatory infiltrates immediately beneath the epithelial cell layer of the gingiva and skin, respectively. Dermatologists are increasingly aware that the epidermal keratinocyte probably contributes to inflammatory disease progression by secreting a number of pro-inflammatory cytokines and expressing various adhesion molecules. In psoriatic lesions, it is now believed that epidermal keratinocytes may also act as antigen-presenting cells and participate directly in the superantigenic activation of T-cell clones, some of which may initiate, contribute to, or maintain the disease process. Although the role of the host response in periodontal disease has been extensively studied over the years, very little is known about the contribution of the gingival keratinocyte to the inflammatory response. The available published information is discussed in this review, and we suggest that, like its epidermal counterpart, the gingival keratinocyte may participate actively in the pathogenesis of periodontal disease.

Epidemiology and diagnosis of HIV-associated periodontal diseases.

A review of periodontal disease as a manifestation of HIV infection suggests a shift in emphasis over the past 5 years. Initially the focus was on newly described forms of periodontal disease (i.e., HIV-associated gingivitis or linear gingival erythema (LGE); HIV-associated periodontitis or necrotizing ulcerative periodontitis (NUP). While the clinical definition of LGE varies from study to study, an association between LGE and Candida infection has been described. Furthermore, the prevalence of NUP is quite low and this disorder is associated with severe immunosuppression. In contrast, the focus today is on the accelerated rate of chronic adult periodontitis occurring in seropositive patients. While the organisms that characterize adult periodontitis in seronegative individuals are present in subgingival plaque from seropositive individuals, reports suggest that atypical pathogens are also present (i.e., Mycoplasma salivarium, Enterobacter cloacae). Recent studies from our laboratory have identified a novel strain of Clostridium isolated from the subgingival plaque of injecting drug users that has pathologic potential. This organism, however, was found in both seropositive and seronegative individuals in this cohort, suggesting an association with lifestyle rather than serostatus. In addition, data has been published examining the local host response in periodontitis in seropositive individuals. Distinctly elevated levels of IgG in gingival crevicular fluid (GCF) have been observed in seropositive patients. Furthermore, data from our laboratory examining inflammatory mediators in GCF (polymorphonuclear leukocyte lysosomal enzyme beta-glucuronidase and the pro-inflammatory cytokine interleukin-1 beta) suggests an altered response in patients with HIV infection. The alteration manifests as the absence of the expected strong correlation between polymorphonuclear leukocyte activity in the gingival crevice and clinical measures of existing periodontal disease, as well as elevated levels of interleukin-1 beta in sites with deeper probing depths. Therefore, it can be concluded that the progression of periodontal disease in the presence of HIV infection is dependent upon the immunologic competency of the host as well as the local inflammatory response to typical and atypical subgingival microorganisms.