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

Author:

Oliveira Sicília Rezende1ORCID,de Arruda José Alcides Almeida1ORCID,Schneider Ayda Henriques2ORCID,Bemquerer Larissa Marques1ORCID,de Souza Rayssa Maria Soalheiro1,Barbim Paula2,de Mattos‐Pereira Gustavo Henrique1ORCID,Calderaro Débora Cerqueira3ORCID,Machado Caio Cavalcante4,Alves Sandra Fukada5ORCID,Moreira Paula Rocha6,de Oliveira Renê Donizeti Ribeiro4,Louzada‐Júnior Paulo4ORCID,Abreu Lucas Guimarães7ORCID,Cunha Fernando Queiroz2ORCID,Silva Tarcília Aparecida1ORCID

Affiliation:

1. Department of Oral Surgery, Pathology and Clinical Dentistry, School of Dentistry Federal University of Minas Gerais Belo Horizonte Minas Gerais Brazil

2. Department of Pharmacology, Ribeirão Preto Medical School University of São Paulo Ribeirão Preto São Paulo Brazil

3. Department of Locomotor Apparatus, Faculty of Medicine Federal University of Minas Gerais Belo Horizonte Minas Gerais Brazil

4. Division of Clinical Immunology, Ribeirão Preto Medical School University of São Paulo Ribeirão Preto São Paulo Brazil

5. Department of BioMolecular Sciences, School of Pharmaceutical Sciences University of São Paulo Ribeirão Preto São Paulo Brazil

6. Department of Morphology, Institute of Biological Sciences Federal University of Minas Gerais Belo Horizonte Minas Gerais Brazil

7. Department of Child and Adolescent Oral Health, School of Dentistry Federal University of Minas Gerais Belo Horizonte Minas Gerais Brazil

Abstract

AbstractAimWe 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 MethodsPeripheral 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.ResultsThe 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.ConclusionsThe release of NETs by circulating neutrophils is associated with RA and periodontitis and is influenced by the presence of the GTG haplotype.

Funder

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Publisher

Wiley

Subject

Periodontics

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