Periodontite associada à artrite reumatoide: o papel das redes extracelulares de neutrófilos (NETs)

Abstract

Neutrophil extracellular traps (NETs) are recognized as one of the relevant mechanisms in the pathogenesis of periodontitis and rheumatoid arthritis (RA). However, the participation of NETs as a linking mechanism between the two diseases remains poorly understood. The main objectives of the work were:1) To investigate the concentration of NETs in saliva, plasma, and in vitro in individuals with RA and healthy controls and the association of NETs with periodontitis and RA activity; 2) To evaluate the impact of non-surgical periodontal treatment on the concentration of NETs in saliva and plasma; 3) To investigate the association between the presence of single nucleotide polymorphisms in the gene coding for the enzyme peptidyl arginine deaminase 4 (PAD4) with RA, in vitro production of NETs, and periodontitis; 4) To systematize the evidence available in the literature on the effect of non-surgical periodontal treatment on the main clinical and laboratory parameters of RA and disease activity score 28 (DAS28). To accomplish Objectives 1 and 2, the concentration of NETs in saliva, plasma, and culture of neutrophils isolated from peripheral blood was determined by identifying the myeloperoxidase (MPO)-DNA complex using the PicoGreen kit®. To accomplish Objective 3, genomic DNA was extracted from peripheral blood mononuclear cells of individuals with RA and healthy controls, and genotyping was performed for single nucleotide polymorphisms PADI4_89, PADI4_90, PADI4_92, and PADI_104. To accomplish the Objective 4, an overview, including systematic reviews that evaluated the effect of non-surgical periodontal treatment on RA parameters, was performed. The search was carried out in the main databases, with no restriction on language or date of publication. A metaanalysis, including data from the primary studies identified in the analyzed systematic reviews, was also performed. For Objectives 1 and 2, individuals with RA and periodontitis showed a higher concentration of NETs in saliva, plasma, and in vitro. Non-surgical periodontal treatment reduced the concentration of NETs in saliva and plasma of individuals with RA. For Objective 3, no association between the presence of polymorphic genotypes and RA was observed. The presence of a homozygous haplotype for the polymorphism was associated with a higher production of NETs in vitro and worse periodontal parameters. For Objective 4, nine systematic reviews were included in the overview. The main outcomes evaluated were DAS28, C-Reactive protein, and/or erythrocyte sedimentation rate. The meta-analysis showed that nonsurgical periodontal treatment resulted in a significant decrease in DAS28. The concentration of NETs in saliva, plasma and culture of peripheral blood neutrophils is associated with RA and periodontitis and may represent the link between the two diseases. Non-surgical periodontal treatment leads to reduced RA activity. Polymorphisms in the PADI4 gene are associated with the in vitro production of NETs and with presence of periodontitis.