title: Serum nitrated nucleosome levels in patients with systemic lupus erythematosus: a retrospective longitudinal cohort study.
abstract: BACKGROUND
  Circulating nucleosomes released from apoptotic cells are important in the pathogenesis of systemic lupus erythematosus (SLE). Both nucleosomes and anti-nucleosome antibodies are deposited in inflamed tissues in patients with SLE. Active inflammation promotes nitration of tyrosine residues on serum proteins. Our hypothesis was that levels of nitrated nucleosomes would be elevated in patients with SLE and could be associated with disease activity. We therefore carried out a retrospective longitudinal study to investigate factors affecting levels of nitrated nucleosomes (NN) in patients with SLE.
  
  
  METHODS
  A novel serum ELISA was developed to measure serum NN and modified to measure serum nitrated albumin (NA). Levels of both NN and NA were measured in 397 samples from 49 patients with SLE followed through periods of disease flare and remission for a mean of 89 months. Anti-nucleosome antibody (anti-nuc) levels were measured in the same samples. The effects of 24 different clinical, demographic and serological variables on NN, NA and anti-nuc levels were assessed by univariable and multivariable analysis.
  
  
  RESULTS
  Patients with SLE had higher mean NN than healthy controls or patients with other autoimmune rheumatic diseases (P =0.01). Serum samples from 18 out of 49 (36.7%) of SLE patients were never positive for NN. This group of 18 patients was characterized by lower anti-double stranded DNA antibodies (anti-dsDNA), disease activity and use of immunosuppressants. In the remaining 63.3%, NN levels were variable. High NN was significantly associated with anti-Sm antibodies, vasculitis, immunosuppressants, hydroxychloroquine and age at diagnosis. NN levels were raised in neuropsychiatric flares. NN levels did not completely parallel NA results, thus providing additional information over measuring nitration status alone. NN levels were not associated with anti-nuc levels.
  
  
  CONCLUSIONS
  NN are raised in a subset of patients with SLE, particularly those who are anti-Sm positive. Elevated NN may be a marker of vascular activation and neuropsychiatric flares in these patients.
authors: Sara
authors: S
authors: Croca
authors: Paul
authors: P
authors: Bassett
authors: Charis
authors: C
authors: Pericleous
authors: Karim Fouad
authors: KF
authors: Alber
authors: David
authors: D
authors: Latchman
authors: David
authors: D
authors: Isenberg
authors: Ian
authors: I
authors: Giles
authors: Anisur
authors: A
authors: Rahman
authors: Yiannis
authors: Y
authors: Ioannou
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology; D008297:Male; D009707:Nucleosomes / Q000276:immunology*; D012189:Retrospective Studies
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D009707:Nucleosomes