Estudo da infecção e resposta imune a Porphyromonas gingivalis e do perfil imunogenético em mestiços brasileiros portadores de periodontite crônica severa. / Study of infection and immune response do Porphyromonas gingivalis and immunegenetic profile in Brazilians of mixed race with chronic severe periodontitis.

AUTOR(ES)
DATA DE PUBLICAÇÃO

2006

RESUMO

Periodontitis is a multifactorial disease that begins and is maintained by the aggression of periodontopathogenic bacteria in the subgingival dental biofilm, whose form of clinical manifestation is dependent on the type of immune-inflammatory response caused by the complex pathogen-host interaction. Among these bacteria, Porphyromonas gingivalis has been associated with the onset and progression of PD, mainly in adult individuals. Furthermore, there are evidences that variations in the hosts immune response are partly under genetic control. In view of this, the following were the aims of this study: ① to identify the presence of Porphyromonas gingivalis in subgingival biofilm; ② to assess the production of IL-10 and IFN-g whole blood cell cultures(WBCC) stimulated with an extract of this bacterium, as well as to determine seric levels of IgA, IgG and sub-classes (IgG1, IgG2,IgG3, IgG4); ③ to assess the polymorphisms of the genes of cytokines IL-1b+3953C/T, TNFa-308G/A, IL-6-174G/C, TGF-b1codons 10T/C and 25G/C, IFN-γ+874T/A and IL-10-1082G/A,-819C/T,-592C/A, and HLA-DR, -DQ, associating these findings with severe chronic periodontitis. Eighty-four non-smoker individuals of both genders, aged from 30 to 50 years, were selected for the study: 43 patients with severe chronic periodontitis(SCP) comprised the case group and 41 individuals without periodontitis (NP), the control group. Clinical periodontal parameters were assessed. Subgingival biofilm samples were collected to identify the presence of P.gingivalis, using the polymerase chain reaction technique (PCR). To identify the mentioned polymorphisms, genomic DNA was extracted from peripheral blood samples, and genotyping was also done by PCR. Of the selected volunteers, taking into account the respective leukogram, WBCC was performed with the blood samples of 35 individuals, 18 from the SCP group and 17 from the NP group, stimulated with bacterial antigens. The cytokine concentrations in the supernatants and the seric immunoglobulins were determined by using the ELISA test. Statistical analysis was done using the t-Student, Man-Whitney and Spearman Correlation and Exact Fisher tests. The presence of P.gingivalis was detected in 29 patients(67.4%) of the patients in the SCP group, while the presence of this periodontopathogen was not observed in any individuals of the NP Group. The tested antigens induced high IL-10, and low IFN-γ concentrations, especially P.gingivalis. WBCC of the SCP group presented significantly higher (p<0.05) IL-10 production than that of the NP group, when it was stimulated with E.coli LPS and P.gingivalis extract. The seric levels of IgG, IgG1, IgG4(p0.001) and IgG2 (p0.05) reactive to P.gingivalis were significantly higher in the SCP group in comparison with the NP group. In the studied polymorphisms, statistically significant differences were found in the allelic, genotypical and phenotypical frequencies among the individuals in the SCP and NP groups as regards the IL-1b+3953(C/T) gene; the homozygote genotype for the allele 1 (CC), phenotype foreseen as low producer, had a significantly higher frequency (p=0.03) in the NP group (81.48%) than in SCP (65%); inversely, and with a trend towards statistical significance (p=0.08), the allele 2 of IL- 1b+3953(T), phenotype foreseen as high producer, was higher in the SCP group (21.25%) than in NP(10.53%). A significantly higher frequency (p<0.05) of allele HLA-DQB1*05 was also observed in the individuals of the NP group in comparison with the SCP group. The high IL-10 and low IFN-γ production in the WBCC stimulated with raw P.gingivalis extract, in the patients of the SCP group, as well as the high levels of anti-Pg IgG4, may suggest that this periodontopathogen deviates the immune response to a Th2 profile. In turn, the results of the polymorphisms suggest that the homozygote genotype for the allele 1 (CC) of IL-1b+3953(C) may be a protection factor and that the allele 2 IL-1b+3953(T) may be a risk factor, and there is also a suggestion that the allele HLA-DQB1*05 may be a genetic protection marker for the development of severe chronic periodontitis in Brazilians of mixed race.

ASSUNTO(S)

igg ifn-γ porphyromonas gingivalis periodontite crônica polimorfismo polymorphism il-10 tnfa hla-dr, -dq chronic periodontitis il-6 resposta imune il-1b immune response imunologia porphyromonas gingivalis tgf-b1

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