title: DNA damage increase in peripheral neutrophils from patients with rheumatoid arthritis is associated with the disease activity and the presence of shared epitope.
abstract: OBJECTIVE
  Neutrophils play a major role in rheumatoid arthritis (RA) pathogenesis. We aimed to evaluate if neutrophil DNA damage in RA patients is associated with the disease activity, autoantibodies status, carriage of the RA shared epitope (SE) and treatment.
  
  
  METHODS
  DNA damage was assessed by alkaline comet assay in peripheral blood (77 patients and 55 healthy controls) and in 10 RA synovial fluid neutrophils. Evaluation of the respiratory burst of 30 patients with RA and 30 healthy controls was done.
  
  
  RESULTS
  Compared to controls, RA patients exhibited increased neutrophil DNA damage. RA synovial fluid cells DNA damage was increased when compared to OA synovial fluids cells. In addition, our study shows that anti-TNF-α therapy reduces the frequency of DNA damage. Patients with simple or double dose of shared epitope presented a higher frequency of DNA damage compared to patients without the allele. Positive correlation was found between neutrophil DNA damage and DAS-28 and ROS production.
  
  
  CONCLUSIONS
  Our results suggest that an increase of respiratory burst of neutrophils reflects the higher levels of DNA damage in neutrophils and a positive correlation between DNA damage and disease activity shows the importance of oxidative stress in the pathogenesis of RA.
authors.affiliation: Program of Basic & Applied Immunol., Faculty Medicine Ribeirão Preto (FMRP-USP), Univ. São Paulo; and Dept. Clinical & Toxicological Analysis, School of Pharmaceutical Sciences, Federal Univ. Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte, Brazil.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Martelli-Palomino
authors.affiliation: Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Adriana B
authors.initials: AB
authors.lastname: Paoliello-Paschoalato
authors.affiliation: Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, Federal University of Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte, Brazil.
authors.forename: Janaina C O
authors.initials: JC
authors.lastname: Crispim
authors.affiliation: Division of Rheumatology, Faculty de Medicine, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Rassi
authors.affiliation: Division of Rheumatology, Faculty de Medicine, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Rene D
authors.initials: RD
authors.lastname: Oliveira
authors.affiliation: Division of Rheumatology, Faculty de Medicine, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Paulo
authors.initials: P
authors.lastname: Louzada
authors.affiliation: Program of Basic and Applied Immunology, and Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Yara Maria
authors.initials: YM
authors.lastname: Lucisano-Valim
authors.affiliation: Program of Basic and Applied Immunology, and Department of Rheumatology, Faculty de Medicine de Ribeirão Preto (FMRP-USP), University of São Paulo Ribeirão Preto, São Paulo, Brazil.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Donadi
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D000939:Epitopes / Q000097:blood / Q000235:genetics / Q000276:immunology*; D005260:Female; D006680:HLA Antigens / Q000097:blood / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D018501:Antirheumatic Agents; D001323:Autoantibodies; D000939:Epitopes; D006680:HLA Antigens; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha