Avaliação de polimorfismos gênicos e da expressão fenotípica de moléculas envolvidas com a resposta imune na doença periodontal

Abstract

Periodontitis is a multifactorial disease associated with inflammation, destruction of periodontal attachment, bone and tooth loss. The presence of Gram-negative bacteria is necessary to initiate and perpetuate periodontitis, but the role of phenotypic and genetic factors in the immune response are essential for maintenance and progression of disease. The aim of present study was to perform a phenotypic and genotypic study of molecules involved with immune response in individuals with different forms of periodontitis in Brazilian population. The specific aims were to investigate the expression of molecules HLA-DR, CD69, CD80, CD86, CD28, CTLA4, IL10, TNF- , IFN- and IL17A from lymphocytes and monocytes in presence or absence of LPS; and to investigate the occurrence of the IL17A (rs2275913), IL17F (rs763780), IL23R (rs11209026), STAT1 (rs3771300), STAT4 (rs7574865) and NFkB1 (rs721412) gene polymorphisms in different clinical forms of periodontitis. To phenotypic study peripheral blood was obtained from 86 non-smoker individuals and analyzed by flow cytometry. Genomic DNA was obtained from oral swabs in 181 individuals and analyzed by Real-Time PCR to perform genotypic study. The study group was composed by individuals without periodontitis (control), with aggressive periodontitis (AP) and with chronic periodontitis (CP). LPS- P.gingivalis was able to increase the frequency and expression intensity of CD80, TNF- and IFN- and decrease of IL10 from CD14+ and CD4+ cells. Even thought the P.gingivalis has been able to reduce the expression of CD86, this molecule also was higher in AP than Control. This result shows the importance of CD86 in immune response of periodontitis. In all groups and conditions the frequency of CD28- was higher than CTLA4+ in CD4+ and CD8+ cells. LPS- E.coli and LPS- P.gingivalis have different influence on co-stimulatory molecules expression. Higher frequency of IL17A+CD4+Tcells was observed in control group. The A+ genotype from IL17A (rs2275913) was associated with lack of disease, and the presence of the G allele for STAT1(rs3771300) was associated with the occurrence of AP, as well as with severity disease. No association was found considering the IL17F, IL23R, STAT4 and NFkB1 polymorphisms. Our data suggest that the A allele of IL17A (rs2275913) is associated with the absence of periodontal disease and G allele for STAT1(rs3771300) with AP. The phenotypic findings produced new questions about the role of different cell subtypes in the immune response of periodontitis.