DOI: 10.1111/jcpe.13921 ISSN: 0303-6979

Neutrophil extracellular traps in rheumatoid arthritis and periodontitis: Contribution of PADI4 gene polymorphisms

Sicília Rezende Oliveira, José Alcides Almeida de Arruda, Ayda Henriques Schneider, Larissa Marques Bemquerer, Rayssa Maria Soalheiro de Souza, Paula Barbim, Gustavo Henrique de Mattos‐Pereira, Débora Cerqueira Calderaro, Caio Cavalcante Machado, Sandra Fukada Alves, Paula Rocha Moreira, Renê Donizeti Ribeiro de Oliveira, Paulo Louzada‐Júnior, Lucas Guimarães Abreu, Fernando Queiroz Cunha, Tarcília Aparecida Silva
  • Periodontics



We sought to investigate the release of neutrophil extracellular traps (NETs) in neutrophils from individuals with rheumatoid arthritis (RA) and controls and compare the presence of NETs in gingival tissues according to periodontal status. Also, the association between single nucleotide polymorphisms (SNPs) of the peptidyl arginine deaminase type 4 (PADI4) gene and the GTG haplotype with RA, periodontitis and NETs was evaluated in vitro.

Materials and Methods

Peripheral neutrophils were isolated by density gradient, and NET concentration was determined by the PicoGreen method. Immunofluorescence was studied to identify NETs by co‐localization of myeloperoxidase (MPO)‐citrullinated histone H3 (H3Cit). Genotyping for SNPs (PADI4_89; PADI4_90; PADI4_92; and PADI4_104) was performed in 87 individuals with RA and 111 controls.


The release of NETs in vitro was significantly higher in individuals with RA and periodontitis and when stimulated with Porphyromonas gingivalis. Gingival tissues from subjects with RA and periodontitis revealed increased numbers of MPO‐H3Cit‐positive cells. Individuals with the GTG haplotype showed a higher release of NETs in vitro and worse periodontal parameters.


The release of NETs by circulating neutrophils is associated with RA and periodontitis and is influenced by the presence of the GTG haplotype.

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