O lúpus eritematoso sistêmico (LES) é uma doença autoimune caracterizada por hiperatividade imunológica crônica pela ação de autoanticorpos que afetam diversos órgãos. Embora o uso crônico de imunossupressores predisponha o paciente a infecções, poucas pesquisas avaliaram uma possível associação entre doença periodontal e LES. Os objetivos deste trabalho foram investigar, por meio de estudo caso-controle, a prevalência e a gravidade da doença periodontal em pacientes com LES, e identificar e quantificar as principais bactérias periodontais presentes no biofilme subgengival. Foram incluídas 60 mulheres em atendimento no Setor de Reumatologia do Hospital Universitário de Brasília, de 20 a 65 anos de idade, sendo subdivididas em LES-A (ativo; n= 31) e LES-I (inativo; n=29). O grupo controle foi composto por 31 mulheres com os mesmos critérios de inclusão, porém sem doenças sistêmicas. As pacientes foram avaliadas quanto às medidas de profundidade de sondagem (P.S), perda de inserção clínica (PIC), índice de sangramento do sulco (ISS) e índice de placa (IPl) no exame inicial. Foram coletados biofilmes subgengivais dos quatro sítios mais profundos para identificação e quantificação de periodontopatógenos por meio de hibridação DNA-DNA checkerboard. Não houve diferenças estatisticamente entre os grupos relativamente aos parâmetros clínicos periodontais, exceto para o ISS, que foi menor no LESA (11,19% ± 14,62%) comparativamente ao grupo controle (17,30% ± 14,88%), porém sem diferenças quando comparado com o grupo LES-I (11,34% ± 11,59%). Houve baixa prevalência de bolsas periodontais, de PIC 4 mm e de espécies de Actinomyces em todos os grupos. Verificou-se aumento na contagem de bactérias do complexo vermelho no grupo LES-I (4,07 x 105; 95% CI: 0,16-0,79) em relação ao grupo controle (2,50 x 105; 95% CI: 1,23-3,77), com diferenças estatisticamente significante apenas referente ao grupo LES-A (p< 0,05; Kruskal Wallis pós-teste Dunn; 0,45 x 105; 95% CI: 0,16-0,79). Os resultados desse estudo demonstraram que os parâmetros periodontais são semelhantes entre pacientes com LES e grupo controle. O grupo de LES-I apresentou maior tempo dessa doença; aumento da contagem de microorganismos (especialmente dos complexos vermelho e verde em amostras de biofilme subgengival) e pior condição periodontal. / Systemic lupus erythematous (SLE) is an autoimmune disorder characterized by chronic immunological hyperactivity resultant from the action of autoantibodies, affecting many organs. Although the use of immune suppressors may predispose infections, few studies have investigated the prevalence and severity of periodontal disease in SLE patients. The aim of this study is to investigate the prevalence and severity of periodontal disease in SLE patients and the sub gingival levels of different pathogens. A total of 60 women attending of Brasília University Hospital, aged 18-65 years, were invited to participate in the study. SLE patients were allocated in two subgroups according with disease activity: SLE-A (active disease; n= 31) and SLE-I (inactive disease; n= 29). A number of 31 systemically healthy women at the same age range composed control group. Patients were clinically examined according to probing depth (PD), clinical attachment level (CAL), sulcular bleeding index (SBI) and plaque index (PLI) at baseline examination. Sub gingival biofilm samples were collected from the deepest four sites before periodontal treatment in order to identify and quantify the level of periodontopathogens by checkerboard DNA-DNA hybridization. No significant differences were found between groups in PD, CAL and PLI. Significant differences were observed in GBI between SLE-A (11,19% ± 14,62%) compared to controls (17,30% ± 14.88%), although with no differences when compared to SLE-I (11,34% ± 11,59%). There was a low prevalence of PD and attachment loss 4 mm at all groups. A low prevalence of Actinomyces was observed at all groups, with an increase in red complex species at LES-I (4,07 x 105; 95% CI: 0,16-0,79) compared to control (2,50 x 105; 95% CI: 1,23-3,77), although with significant differences (p< 0,05; Kruskal Wallis post hoc Dunn) only when compared to SLE-A (0,45 x 105; 95% CI: 0,16-0,79). These findings show no differences in the periodontal conditions of SLE compared to systemically healthy patients, except for a decrease in gingival bleeding index, especially at SLE-A. Reductions in microorganisms count were observed at SLE-A, while an increase in bacterial count, especially at red and green complex, were observed at subgingival biofilm of SLE-I patients.

O lúpus eritematoso sistêmico (LES) é uma doença autoimune caracterizada por hiperatividade imunológica crônica pela ação de autoanticorpos que afetam diversos órgãos. Embora o uso crônico de imunossupressores predisponha o paciente a infecções, poucas pesquisas avaliaram uma possível associação entre doença periodontal e LES. Os objetivos deste trabalho foram investigar, por meio de estudo caso-controle, a prevalência e a gravidade da doença periodontal em pacientes com LES, e identificar e quantificar as principais bactérias periodontais presentes no biofilme subgengival. Foram incluídas 60 mulheres em atendimento no Setor de Reumatologia do Hospital Universitário de Brasília, de 20 a 65 anos de idade, sendo subdivididas em LES-A (ativo; n= 31) e LES-I (inativo; n=29). O grupo controle foi composto por 31 mulheres com os mesmos critérios de inclusão, porém sem doenças sistêmicas. As pacientes foram avaliadas quanto às medidas de profundidade de sondagem (P.S), perda de inserção clínica (PIC), índice de sangramento do sulco (ISS) e índice de placa (IPl) no exame inicial. Foram coletados biofilmes subgengivais dos quatro sítios mais profundos para identificação e quantificação de periodontopatógenos por meio de hibridação DNA-DNA checkerboard. Não houve diferenças estatisticamente entre os grupos relativamente aos parâmetros clínicos periodontais, exceto para o ISS, que foi menor no LESA (11,19% ± 14,62%) comparativamente ao grupo controle (17,30% ± 14,88%), porém sem diferenças quando comparado com o grupo LES-I (11,34% ± 11,59%). Houve baixa prevalência de bolsas periodontais, de PIC 4 mm e de espécies de Actinomyces em todos os grupos. Verificou-se aumento na contagem de bactérias do complexo vermelho no grupo LES-I (4,07 x 105; 95% CI: 0,16-0,79) em relação ao grupo controle (2,50 x 105; 95% CI: 1,23-3,77), com diferenças estatisticamente significante apenas referente ao grupo LES-A (p< 0,05; Kruskal Wallis pós-teste Dunn; 0,45 x 105; 95% CI: 0,16-0,79). Os resultados desse estudo demonstraram que os parâmetros periodontais são semelhantes entre pacientes com LES e grupo controle. O grupo de LES-I apresentou maior tempo dessa doença; aumento da contagem de microorganismos (especialmente dos complexos vermelho e verde em amostras de biofilme subgengival) e pior condição periodontal. / Systemic lupus erythematous (SLE) is an autoimmune disorder characterized by chronic immunological hyperactivity resultant from the action of autoantibodies, affecting many organs. Although the use of immune suppressors may predispose infections, few studies have investigated the prevalence and severity of periodontal disease in SLE patients. The aim of this study is to investigate the prevalence and severity of periodontal disease in SLE patients and the sub gingival levels of different pathogens. A total of 60 women attending of Brasília University Hospital, aged 18-65 years, were invited to participate in the study. SLE patients were allocated in two subgroups according with disease activity: SLE-A (active disease; n= 31) and SLE-I (inactive disease; n= 29). A number of 31 systemically healthy women at the same age range composed control group. Patients were clinically examined according to probing depth (PD), clinical attachment level (CAL), sulcular bleeding index (SBI) and plaque index (PLI) at baseline examination. Sub gingival biofilm samples were collected from the deepest four sites before periodontal treatment in order to identify and quantify the level of periodontopathogens by checkerboard DNA-DNA hybridization. No significant differences were found between groups in PD, CAL and PLI. Significant differences were observed in GBI between SLE-A (11,19% ± 14,62%) compared to controls (17,30% ± 14.88%), although with no differences when compared to SLE-I (11,34% ± 11,59%). There was a low prevalence of PD and attachment loss 4 mm at all groups. A low prevalence of Actinomyces was observed at all groups, with an increase in red complex species at LES-I (4,07 x 105; 95% CI: 0,16-0,79) compared to control (2,50 x 105; 95% CI: 1,23-3,77), although with significant differences (p< 0,05; Kruskal Wallis post hoc Dunn) only when compared to SLE-A (0,45 x 105; 95% CI: 0,16-0,79). These findings show no differences in the periodontal conditions of SLE compared to systemically healthy patients, except for a decrease in gingival bleeding index, especially at SLE-A. Reductions in microorganisms count were observed at SLE-A, while an increase in bacterial count, especially at red and green complex, were observed at subgingival biofilm of SLE-I patients.

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Le lymphocyte B (LB) des patients lupiques est réfractaire à tous les procédés décrits à ce jour pour activer une fonction régulatrice B (Breg). Il constitue de ce fait un modèle intéressant d’étude de la déficience Breg chez l’Homme et soulève de nombreuses interrogations. Est-il possible de restaurer un défaut d’activation de la régulation LB? Si oui est-il possible d'agir à temps et le plus efficacement possible, et comment s'y prendre? Ou au contraire, est-ce un état irréversible de la cellule B? Ce travail de thèse a pour objectif principal de répondre à cette problématique essentielle à notre compréhension du Breg. Grace à un polypeptide de synthèse le Glatiramer acetate (GA), nous montrons que la restauration de la fonction régulatrice d’un Breg chez les patients lupiques est possible. Le compartiment LB mémoire fixe fortement le GA et la pré-sensibilisation par le GA permet d’augmenter le potentiel régulateur des LB mémoires mais n’affecte aucunement celui des LB matures. Le GA exerce deux actions majeures sur le LB mémoire. D’une part, il génère une meilleure capacité d’inhibition de la prolifération T, dont le mécanisme est associé à un contact cellulaire impliquant les molécules HLA-DR. D’autre part, il favorise un contrôle plus efficace de la polarisation Th1 qui est très probablement associé à sa capacité à induire la production d’IL-10 dans ces LB. Enfin, le GA modifie le phénotype des LB mémoires puisque l’expression de CD5, IL-21R, ou encore PD-1 est significativement augmentée, autant de molécules impliquées dans la fonction suppressive et dans la production d’IL-10. En conclusion, nous montrons qu’amplifier une fonction régulatrice et surtout la restaurer lorsqu’elle est défaillante chez les malades, est parfaitement possible in vitro. Face à l’engouement suscité par le développement de procédés favorisant l’expansion des Bregs chez la souris à des fins thérapeutiques, l’enjeu est aujourd’hui d’être en mesure d’extrapoler de telles démarches chez l’Homme. Ce travail, avec toute la modestie requise, contribuera à faire naître un nouvel élan vers de telles perspectives. / B cell in systemic lupus erythematous (SLE) is unresponsive to all methods described to date, to activate B cells regulatory (Breg) function. Therfore, it is an interesting model to study the Breg deficiency in Human, and highlights many questions: is there a way to restore a defect of the Breg activation ? If yes, how can we act more efficiently ? Or in contrast, is it an irreversible state of the B cell? Glatiramer Acetate (GA) is a synthetic polypeptide used in the treatment of multiple sclerosis. We show that Breg activity of SLE B cells can be restored after stimulation with GA. Interestingly, memory B cells bound high level of FITC-conjuated GA in contrast to mature B cells. We desmonstrate that GA can increased specifically the regulatory activities of memory B cells. GA exerts two major actions on the memory B cells. It generates an improved capacity of inhibition of the T cell proliferative response, whose mechanism is associated with a cellular contact involving HLA-DR molecules. In addition, GA supports a more effective control of the Th1 polarization which is most likely associated with its capacity to induce the production of IL-10 in these B cells. Finaly, GA modifies the memory B cell phenotype since the expression CD5, IL-21R, or PD-1 is significantly increased, all molecules involved in the suppressive function and the IL-10 production. In conclusion, our results show for the first time that amplification of Breg function and additionally its restoration when it is defective in patients, can be perfectly achieved in vitro. Currently, while the development of new process supporting the expansion of Bregs in the mouse model exist, the challenge is to extrapolate such methods in human. Through the control of their regulatory potential, regulatory B cells could be the targets of novel therapeutic approach in autoimmune diseases. This study might open up new horizons in this field.