Immunolocalization of matrix metalloproteinases-2 and-9 during apical periodontitis development

Objective: The objective of this study was to determine the expression of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) during apical periodontitis development. Methods: Using an experimental design of induced periapical lesions in rats and immunohistochemistry assay as investigative tool, the MMP-2 and MMP-9 expression and distribution were evaluated at 3, 7,14, 21, 30,60 and 90 days after coronary access and pulp exposure of the first left mandibular molar to the oral environment. Two blind observers scored the immunoreactivity. A semi-quantitative analysis was performed. Results: Except at day 3, MMP-2 and MMP-9 immunostaining was observed in all experimental periods. The MMP-2 (p = 0.004) and MMP-9 (p = 0.005) immunostaining was higher in the period between 7 and 21 days. They were mainly observed in cells surrounding the apical foramen and adjacent periapical areas. Cells into the hypercementosis areas were strongly stained while both osteoblasts and osteoclasts; presented discrete staining along of this study. No staining was observed on epithelial walls. At 30, 60 and 90 days, the subjacent connective tissue presented intense MMP-2 and MMP-9 immunostaining in mononuclear cells (suggestive of fibroblasts, macrophages, infiltrating neutrophils and lymphocytes). Conclusion: The results observed in this study suggest that MMP-2 and MMP-9 play a critical role in the development of inflammatory periapical lesions, probably involved in the extracellular matrix (ECM) degradation during the initial phase of the lesion development. (C) 2009 Elsevier Ltd. All rights reserved.

COX-2 inhibition decreases VEGF expression and alveolar bone loss during the progression of experimental periodontitis in rats

Background: Vascular endothelial growth factor (VEGF) is a macromolecule of importance in inflammation that has been implicated in periodontitis. The aims of this study were to investigate VEGF expression during the progression of periodontal disease and to evaluate the effect of a preferential cyclooxygenase (COX)-2 inhibitor meloxicam on VEGF expression and alveolar bone loss in experimentally induced periodontitis. Methods: A total of 120 Wistar rats were randomly separated into groups 1 (control) and 2 (meloxicam, 3 mg/kg/day, intraperitoneally, for 3, 7, 14, or 30 days). Silk ligatures were placed at the gingival margin level of the lower right first molar of all rats. VEGF expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR), Western blot (WB), and immunohistochemical (IHC) analyses. The hemiarcades were processed for histopathologic analysis. RT-PCR and WB results were submitted to analysis of variance, the Tukey test, and Pearson correlation analysis (P<0.05). Results: A reduction in alveolar bone resorption was observed in the meloxicam-treated group compared to the control group at all periods studied. There was a positive correlation between COX-2 mRNA and VEGF mRNA in the gingival tissues and periodontal disease (R = 0.80; P = 0.026). Meloxicam significantly reduced the increased mRNA VEGF expression in diseased tissues after 14 days of treatment (P = 0.023). Some alterations in VEGF receptor I mRNA expression were observed, but these were not statistically significant. VEGF protein expression in WB experiments was significantly higher in diseased sites compared to healthy sites (P<0.05). After 14 days of treatment with meloxicam, an important decrease in VEGF protein expression was detected in diseased tissues (P = 0.08). Qualitative IHC analysis revealed that VEGF protein expression was higher in diseased tissues and decreased in tissues from rats treated with meloxicam. Conclusions: The present data suggest an important role for VEGF in the progression of periodontal disease. Systemic therapy with meloxicam can modify the progression of experimentally induced periodontitis in rats by reducing VEGF expression and alveolar bone loss.

Influence of Antiplatelet Drugs in the Pathogenesis of Experimental Periodontitis and Periodontal Repair in Rats

Background: Platelets contain an array of biologic mediators that can modulate inflammation and repair processes including proinflammatory mediators and growth factors. Previous studies have shown that periodontitis and periodontal repair are associated with platelet activation. We hypothesized that drug-induced platelet inactivation may interfere in the processes of inflammation and repair in experimental periodontitis in rats by suppressing the release of biologic mediators from platelets to the site of injury. Methods: To measure the effects on periodontitis, ligatures were placed around first molars, and aspirin (Asp, 30 mg/kg) or clopidogrel (Clo, 75 mg/kg) was given intragastrically once daily for 15 days. Interleukin-6 (IL-6), tumor necrosis factor-a (TNF-alpha), and thromboxane A(2) levels were measured by enzyme-linked immunosorbent assay. To evaluate the effects of antiplatelet drugs on periodontal repair, ligatures were removed after 15 days of periodontitis induction, and Asp or Clo were administered beginning the following day for 15 days. Periodontal repair was assessed by microcomputed tomography. Results: On periodontitis phase, Asp and Clo significantly reduced levels of TNF-alpha and II-6 (P < 0.05), but only Asp decreased thromboxane A(2) (P < 0.05). Asp and Clo decreased inflammatory infiltration; however, this reduction was more pronounced with Clo treatment (P < 0.05). Histometric analysis showed that Asp and Clo impaired alveolar bone resorption. During the repair phase and after removal of the ligatures, microcomputed tomography analysis demonstrated that treatment with Asp and Clo did not impair alveolar bone repair. Conclusion: Systemic administration of Asp and Clo attenuates the inflammation associated with periodontitis without affecting the repair process when stimulus is removed. J Periodontol 2011;82:767-777.

Destructive periodontitis lesions are determined by the nature of the lymphocytic response

It is now 35 years since Brandtzaeg and Kraus (1965) published their seminal work entitled Autoimmunity and periodontal disease. Initially, this work led to the concept that destructive periodontitis was a localized hypersensitivity reaction involving immune complex formation within the tissues. In 1970, Ivanyi and Lehner highlighted a possible role for cell-mediated immunity, which stimulated a flurry of activity centered on the role of lymphokines such as osteoclast-activating factor (OAF), macrophage-activating factor (MAF), macrophage migration inhibition factor (MIF), and myriad others. In the late 1970s and early 1980s, attention focused on the role of polymorphonuclear neutrophils, and it was thought that periodontal destruction occurred as a series of acute exacerbations. As well, at this stage doubt was being cast on the concept that there was a neutrophil chemotactic defect in periodontitis patients. Once it was realized that neutrophils were primarily protective and that severe periodontal destruction occurred in the absence of these cells, attention swung back to the role of lymphocytes and in particular the regulatory role of T-cells. By this time in the early 1990s, while the roles of interleukin (IL)-1, prostaglandin (PG) E-2, and metalloproteinases as the destructive mediators in periodontal disease were largely understood, the control and regulation of these cytokines remained controversial. With the widespread acceptance of the Th1/Th2 paradigm, the regulatory role of T-cells became the main focus of attention, Two apparently conflicting theories have emerged. One is based on direct observations of human lesions, while the other is based on animal model experiments and the inability to demonstrate IL-4 mRNA in gingival extracts. As part of the Controversy series, this review is intended to stimulate debate and hence may appear in some places provocative. In this context, this review will present the case that destructive periodontitis is due to the nature of the lymphocytic infiltrate and is not due to periodic acute exacerbations, nor is it due to the so-called virulence factors of putative periodontal pathogens.

Accumulation of human heat shock protein 60-reactive T cells in the gingival tissues of periodontitis patients

Heat shock protein 60s (hsp60) are remarkably immunogenic, and both T-cell and antibody responses to hsp60 have been reported in various inflammatory conditions. To clarify the role of hsp60 in T-cell responses in periodontitis, we examined the proliferative response of peripheral blood mononuclear cells (PBMC), as well as the cytokine profile and T-cell clonality, for periodontitis patients and controls following stimulation with recombinant human hsp60 and Porphyromonas gingivalis GroEL. To confirm the infiltration of hsp60-reactive T-cell clones into periodontitis lesions, nucleotide sequences within complementarity-determining region 3 of the T-cell receptor (TCR) beta-chain were compared between hsp60-reactive peripheral blood T cells and periodontitis lesion-infiltrating T cells. Periodontitis patients demonstrated significantly higher proliferative responses of PBMC to human hsp60, but not to P. gingivalis GroEL, than control subjects. The response was inhibited by anti-major histocompatibility complex class 11 antibodies. Analysis of the nucleotide sequences of the TCR demonstrated that human hsp60-reactive T-cell clones and periodontitis lesion-infiltrating T cells have the same receptors, suggesting that hsp60-reactive T cells accumulate in periodontitis lesions. Analysis of the cytokine profile demonstrated that hsp60-reactive PBMC produced significant levels of gamma interferon (IFN-gamma) in periodontitis patients, whereas P. gingivalis GroEL did not induce any, skewing toward a type1 or type2 cytokine profile. In control subjects no significant expression of IFN-gamma or interleukin 4 was induced. These results suggest that periodontitis patients have human hsp60-reactive T cells with a type I cytokine profile in their peripheral blood T-cell pools.

Periodontitis and gingivitis in inflammatory bowel disease: a case-control study.

BACKGROUND: The oral cavity is frequently affected in patients with inflammatory bowel disease (IBD), especially in patients with Crohn's disease (CD). Periodontitis is thought to influence systemic autoimmune or inflammatory diseases. We aimed to analyze the relationship of periodontitis and gingivitis markers with specific disease characteristics in patients with IBD and to compare these data with healthy controls. METHODS: In a prospective 8-month study, systematic oral examinations were performed in 113 patients with IBD, including 69 patients with CD and 44 patients with ulcerative colitis. For all patients, a structured personal history was taken. One hundred thirteen healthy volunteers served as a control group. Oral examination focussed on established oral health markers for periodontitis (bleeding on probing, loss of attachment, and periodontal pocket depth) and gingivitis (papilla bleeding index). Additionally, visible oral lesions were documented. RESULTS: Both gingivitis and periodontitis markers were higher in patients with IBD than in healthy control. In univariate analysis and logistic regression analysis, perianal disease was a risk factor for periodontitis. Nonsmoking decreased the risk of having periodontitis. No clear association was found between clinical activity and periodontitis in IBD. In only the CD subgroup, high clinical activity (Harvey-Bradshaw index > 10) was associated with 1 periodontitis marker, the loss of attachment at sites of maximal periodontal pocket depth. Oral lesions besides periodontitis and gingivitis were not common, but nevertheless observed in about 10% of patients with IBD. CONCLUSIONS: IBD, and especially perianal disease in CD, is associated with periodontitis. Optimal therapeutic strategies should probably focus on treating both local oral and systemic inflammation.

Role of protease-activated receptor-2 in inflammation, and its possible implications as a putative mediator of periodontitis

Proteinase-activated receptor-2 (PAR2) belongs to a novel subfamily of G-protein-coupled receptors with seven-transmembrane domains. This receptor is widely distributed throughout the body and seems to be importantly involved in inflammatory processes. PAR2 can be activated by serine proteases such as trypsin, mast cell tryptase, and bacterial proteases, such as gingipain produced by Porphyromonas gingivalis. This review describes the current stage of knowledge of the possible mechanisms that link PAR2 activation with periodontal disease, and proposes future therapeutic strategies to modulate the host response in the treatment of periodontitis.

Experimental bacterial endocarditis after dental extractions in rats with periodontitis.

The development of bacterial endocarditis was analyzed after dental extractions in rats with or without periodontal disease. Periodontal disease was produced in rats by tying silk ligatures around the two maxillary first molars and placing the animals on a high sucrose diet for 14 weeks. Sterile aortic valve vegetations were produced by means of a transaortic catheter, and 24 hr later the maxillary first molars were extracted. The animals were killed 72 hr after the extractions. In rats with periodontal disease, extractions resulted in a 48% (14 of 29) incidence of bacterial endocarditis, most cases of which were due to Streptococcus spp. (one was caused by Staphylococcus aureus). In contrast, when the teeth with a healthy periodontium were extracted, only 6% (one of 15) of the rats developed endocarditis. When catheters were placed in animals with periodontal disease but no extractions were performed, no endocarditis occurred.

Experimental endocarditis following dental extractions in rats with periodontitis.

This study analyzed the development of bacterial endocarditis following dental extraction in rats with periodontal disease. Periodontal disease was produced in rats by tying silk ligatures around the two maxillary first molars, and placing the animals on a high sucrose diet. Sterile aortic valve vegetations were produced by means of a transaortic catheter, and 24 hours later the maxillary first molars were extracted. The animals were killed 72 hours after the extractions. In rats with periodontal disease induced for 10 and 14 weeks, extractions resulted in an incidence of bacterial endocarditis of 24% and 50%, respectively, most of which were due to streptococcal species (two were caused by Staphylococcus [corrected] aureus). The difference, though not statistically significant (p = 0.10, chi 2 with Yates correction), shows a trend toward increased incidence of endocarditis with increasing severity of periodontal disease. This model demonstrates that one can reliably induce bacterial endocarditis after dental extractions in rats with periodontal disease.

Introduced ants in Galápagos (Floreana Island) : importance of competition, coexistence and agressive behaviors

Abstract Invasive species represent with fragmentation of habitat the most serious threats to biodiversity in the world. Galápagos Archipelago, as most oceanic islands, suffers a high rate of introduced animals and plants that affect equilibrium and biodiversity of this unique biota. Ants rank among the most devastating invaders. Their social organization confer them a high ability to adapt and to spread in new environments forming rapidly populous communities. We studied the ant community of Floreana Island composed mainly of introduced species (at least 1 S). Introduction events occurred successively during last century. The last record is Monomorium destructor arrived in the eighties. Our aim is to investigate the modalities of interaction and coexistence of these introduced species. We highlighted the competition hierarchy of the coexisting species using attractive food baits. Two species behave as competitively dominant by monopolizing an important part of resources. They are M. destructor restricted to a small area and the fire ant Solenopsis geminata widely distributed on the island. Then we evaluated the relative importance of abiotic factors and interspecific competition in structuring the community. Ecological data were collected and presence and abundance of species were estimated using different methods in a wide range of habitats. Several species showed preferences either for arid or for humid areas. The little fire ant Wasmannia auropunctata, awell-known devastating species when introduced, was exclusively found in moist habitat in and around the agricultural area situated in the upper and central part of thé island. It coexists with other species in several parts but in a restricted perimeter it excludes all other ants and worker's density on the ground is nearly 70 times higher than ant's density in similar habitats occupied by several species. But most opportunist tramp species establish everywhere without particular ecological requirement. Analyses of species co-occurrences at various levels didn't reveal any marked effect of competition in structuring ant's assemblages. We supposed that the lack ofcompetition-derived structure has to be attributed to the dynamic of the system. Indeed, across the successive census of 1996, 2003, 2004 and 2005, species distributions and abundances appeared to be highly variables. In particular harsh conditions occurring in dry season in certain parts seem to be limiting to S. geminatai. We suggest that huge variations in the local distribution of the dominant S. geminata disrupt the community organization. Finally we conducted artificial ant confrontations to evaluate to what extend an aggressive behavior at the worker level maybe linked to the ecological success of a species on the island. S. geminata was rather indifferent when confronted to a submissive species on food sources, suggesting that its competitive dominance is largely due to a numerical superiority. On the other hand M. destructor exhibits a strong agonistic behavior in similar confrontations. As soon as the presence of a competitor is detected, most workers were observed to abandon foraging and to take part in physical aggressions. Since it is still restricted nearby its introduction spot two decades after its arrival, we suggest that the energetic cost of such an aggressive behavior prevent it to spread on that island already highly colonized. Dominant invasive species such as the fire ants S. geminata and W. auropunctata have negative impacts on Galápagos fauna, disturbing the hatching of land tortoises and birds. But very little is known about the impact of other exotic ants. Indeed, impact on arthropods and generally on ground-dwelling organisms is very diffcult to evaluate. As a consequence of the dynamic character of Floreana I. ant community it is difficult to build models or to málce predictions on evolution of introduced ant fauna. But Camponotus macilentus, an abundant endemic species seems today to be little affected by introduced ant species thanks to its strong interference competition ability and its preference for arid and harsh environments. Résumé Les espèces envahissantes représentent, avec la fragmentation du paysage, la plus grande menace pour la biodiversité. L'archipel des Galápagos, comme la plupart des îles du Pacifique, compte un grand nombre d'espèces introduites qui menacent la biodiversité de ce milieu unique.. Les fourmis sont parmi les envahisseurs les plus dévastateurs. Leur organisation sociale leur permet de s'adapter et de se propager pour devenir rapidement abondantes. Nous avons étudié la communauté de fourmis sur l'île de Floreana principalement composée d'espèces introduites (au moins 15). Les introductions se sont succédées au cours du siècle précédent. La dernière espèce recensée est Monomorium destructor introduite dans les années 80. Notre objectif est de mettre à jour les modalités des interactions et de la coexistence de ces espèces introduites. Nous avons mis en évidence la hiérarchie de compétition des différentes espèces à l'aide d'appâts de nourriture. Deux espèces se comportent de façon dominante en monopolisant une part importante des ressources. Ce sont M. destructor, restreintes à un petit périmètre, et la fourmi de feu Solenopsis geminata, largement distribuée sur l'île. Nous avons évalué l'importance relative des facteurs abiotiques et de la compétition interspécifique dans la structuration des peuplements. Des données écologiques ont été collectées et la présence et l'abondance des espèces ont été estimées à l'aide de trois méthodes au sein d'une grande diversité d'habitats. Plusieurs espèces .montrent des préférences soit pour les milieux humides, soit pour les milieux arides. La petite fourmi de feu Wasmannia auropunctata, une espèce connue pour être dévastatrice dans ses sites d'introduction, est présente exclusivement dans les habitats humides dans et à proximité de la zone agricole située dans la partie centrale de l'île. Elle coexiste en plusieurs points avec d'autres espèces mais au sein d'un périmètre restreint elle exclut toute autre fourmi et atteint des densités record au sol presque 70 fois supérieures aux densités de fourmis observées sur les sites voisins occupés par plusieurs espèces. Mais la plupart des espèces vagabondes opportunistes s'établissent partout sans exigences écologiques particulières. Des analyses de cooccurrence d'espèces à plusieurs niveaux n'ont pas révélé de rôle marqué de la compétition dans la structuration des communautés. Nous supposons que l'absence d'une telle structure doit être attribuée à la dynamique du système. En effet, au cours des différents recensements de 1996-1997, 2003, 2004 et 2005, la distribution et l'abondance des espèces était très variable. En particulier, les conditions rudes qui règnent dans la zone aride durant la saison sèche semblent affecter particulièrement S. geminata. Nous suggérons que de fortes variations dans la distribution de l'espèce dominante perturbent l'orgaiùsation des communautés. Finalement nous avons effectué des confrontations artificielles pour évaluer dans quelle mesure un comportement agressif au niveau de l'ouvrière peut être lié au succès écologique d'une espèce sur l'île. S. geminata montre très peu de réaction face à une espèce subordonnée sur une même source de nourriture, ce qui laisse supposer que sa dominance est largement due à sa supériorité numérique. Par contre, dans des conditions similaires, M. destructor est fortement agressive. En présence d'un compétiteur, la plupart des ouvrières renoncent très vite à leur activité de fourragement pour agresser les individus de l'autre espèce. Puisque deux décennies après son introduction elle est toujours confinée à son point d'arrivée, nous supposons que le coût en énergie et en ouvrières de ce comportement très agressif est un obstacle à son expansion sur cette île déjà fortement colonisée. Les espèces envahissantes dominantes comme les fourmis de feu S. geminata et W. auropunctata sont connues pour leur impact négatif sur la faune des Galápagos, entre autre sur les jeunes des tortues terrestres et des oiseaux. Mais nous savons très peu de choses sur l'impact des autres espèces de fourmis introduites. En effet, l'impact sur les arthropodes, et plus généralement sur la faune du sol, est très difficile à évaluer. En raison du caractère dynamique de la communauté de fourmi de Floreana, il est difficile de construire des modèles et de faire des prédictions sur l'évolution des peuplements de fourmis introduites. Mais Camponotus macilentus, une espèce endémique abondante, semble aujourd'hui peu affectée par les espèces introduites grâce à ses capacités de compétition par interférence et sa préférence pour les milieux arides. Resumen Las, especies invasoras representan, junto con la fragmentación del paisaje, la mayor amenaza para la biodiversidad. El archipiélago de Galápagos, como la mayoría de las islas del Pacífico, cuenta con un gran número de especies introducidas que amenazan la biodiversidad de este lugar único. Las hormigas son uno de los invasores más devastadores. Su organización social les permite adaptarse y propagarse para ser rápidamente abundante. Estudiamos la comunidad de hormigas de la isla Floreana principalmente compuesta de especies introducidas (al menos 15). Las introducciones se sucedieron durante el siglo anterior. La última especie contabilizada es Monomorium destructor introducida en los años 80. Nuestro objetivo es poner al día las modalidades de las interacciones y de la coexistencia de estas especies introducidas. Pusimos de relieve la jerarquía de competencia de las distintas especies con ayuda de cebos de comida. Dos especies se implican de manera dominante monopolizando una parte importante de los recursos. Son M. destructor, limitado a un pequeño perímetro, y la hormiga de fuego Solenopsis geminata; ampliamente distribuida por la isla. Evaluamos la importancia relativa de los factores abióticos y de la competencia interespecífica en la estructuración de la communidad. Se recogieron algunos datos ecológicos y se consideraron la presencia y la abundancia de las especies con ayuda de tres métodos en una gran diversidad de hábitats. Varias especies muestran preferencias o por los medios húmedos, o por los medios áridos. La pequeña hormiga de fuego Wasmannia auropunctata, una especie conocida por ser devastadora en sus lugares de introducción, está presente exclusivamente en los hábitats húmedos y cerca de la zona agrícola situada en la parte central de la isla. Coexiste en varios puntos con otras especies pero en un perímetro limitado excluye a cualquier otra hormiga y alcanza densidades en el suelo casi 70 veces superiores a las densidades de hormigas observadas en los lugares vecinos ocupados por varias especies. Pero la mayoría de las especies vagabundas oportunistas se establecen por todas partes sin exigencias ecológicas particulares. Análisis de cooccurrencía de las especies a varios niveles no revelaron una grande importancía de la competencia en la estructuración de las comunidades. Suponemos que la ausencia de tal estructura Bebé ser por la dinámica del sistema. Efectivamente, durante los distintos censos de 1996-1997, 2003,.2004 y 2005, la distribución ? la abundancia de las especies eran muy variables. En particular, las condiciones drásticas que reinan en la zona árida durante la temporada seca parecen afectar especialmente a S. geminata. Sugerimos que fuertes variaciones en la distribución de la especie dominante perturben la organización de las comunidades. Finalmente efectuamos confrontaciones artificiales para evaluar hastá que punto un comportamiento agresivo a nivel de la obrera puede explicar el éxito ecológico de una especie en la isla. S. geminata muestra muy poca reacción ante una especie subordinada mientras comparten la misma comida, lo que deja suponer que su dominancia se debe a su superioridad numérica. Por el contrario, en condiciones similares, M. destructor es muy agresivo. En presencia de otra especie, la mayóría de las obreras renuncian muy rápidamente a alimentarse para atacar a los individuos de la otra especie. Puesto que dos décadas después de su introducción todavía se confina en su punto de llegada, suponemos que el coste en energía y en obreras de este comportamiento muy agresivo es un obstáculo a su extensión en esta isla ya muy colonizada. Las especiés invasoras dominantes como las hormigas de fuego S. geminata y W. auropunctata son conocidas por su impacto negativo en la fauna de Galápagos, entre otras cosas sobre los juveniles de las tortugas terrestres y pájaros. Pero sabemos muy poco sobre el impacto de las otras especies de hormigas introducidas. Efectivamente es muy difïcil de evaluar el impacto en los artrópodos, y más generalmente en la fauna del suelo. Debido al carácter dinámico de la comunidad de hormiga de Floreana, es diEcil construir modelos y hacer predicciones sobre la evolución de las poblaciones de hormigas introducidas. Pero Camponotus macilentus, una especie endémica abundante, parece poco afectadá hoy por las especies introducidas gracias a sus capacidades de competencia por interferencia y su preferencia por los medios áridos.

Periodontitis crónica del adulto y alteraciones inmunitarias

El hecho de que las alteraciones inmunitarias están implicadas en la enfermedad periodontal está ampliamente recogido en la literatura. No obstante la naturaleza exacta y la implicación de las mismas no está clara. Por otro lado el empleo de la citometría de flujo ha posibilitado un avance importante en las técnicas de investigación biomédica y en el caso concreto que nos ocupa la posibilidad de determinar diferentes marcadores monoclonales en la línea celular linfocítica. Estudiamos los marcadores monoclonales (CD4, CDB, CD3 y CD19) en 15 pacientes afectados de enfermedad periodontal avanzada. Los resultados obtenidos se encuentran dentro de los límites de normalidad. Si bien no hemos obtenido datos significativos creemos que la muestra es pequeña y sería útil realizar estudios más amplios y a ser posible a nivel local. No obstante pensamos que lo novedoso es el estudio de anticuerpos monoclonales en relacióncon la enfermedad periodontal, datos que no hemos encontrado en la literatura.