title: Urinary levels of high mobility group box-1 are associated with disease activity in antineutrophil cytoplasmic autoantibody-associated vasculitis.
abstract: BACKGROUND
  High mobility group box-1 (HMGB1), a kind of pro-inflammatory mediator, is associated with inflammatory conditions and tissue damage. Our previous study demonstrated that the circulating levels of HMGB1 correlated with disease activity of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In the current study, we aimed to measure urinary levels of HMGB1 in AAV patients, correlated them to clinical activity index and analysed the immunohistochemical HMGB1 staining in kidney specimens.
  
  
  METHODS
  50 patients with AAV in active stage and 56 patients with AAV in remission were recruited. The urinary levels of HMGB1 were determined by enzyme-linked immunosorbent assay. Moreover, renal biopsy specimens from 27 patients with active AAV were randomly collected to evaluate the deposition of HMGB1.
  
  
  RESULTS
  Urinary HMGB1 levels in AAV patients in active stage were significantly higher than those in AAV patients in remission and healthy controls (1.46 [0.56-3.43] versus 0.38 [0.10-1.35] mg/μmolCr, P=0.001; 1.46 [0.56-3.43] versus 0.48 [0.40-0.60] mg/μmolCr, P=0.000, respectively). Further analysis found that urinary levels of HMGB1 correlated with erythrocyte sedimentation rate (r=0.354, p=0.012), C-reactive protein (r=0.289, p=0.042), and Birmingham Vasculitis Activity Score (r=0.350, p=0.013). Renal tissue of active AAV patients showed HMGB1 was mainly expressed in the cytoplasm and the extracellular space. The percentage of HMGB1-negative nuclei in renal tissue of patients with active AAV was significantly higher than that in normal controls (60.6±20.2 % versus 2.7±0.6 %, p<0.01).
  
  
  CONCLUSIONS
  Urinary levels of HMGB1 may be associated with the disease activity in AAV patients.
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
authors.forename: Tian-Tian
authors.initials: TT
authors.lastname: Ma
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
authors.forename: Dong-Yuan
authors.initials: DY
authors.lastname: Chang
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Zhao
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
mesh_terms: D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000652:urine*; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism / Q000652:urine*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human