title: Alternative complement pathway activation products in urine and kidneys of patients with ANCA-associated GN.
abstract: OBJECTIVE
  Previous study revealed that complement activation products of the alternative pathway could be detected in renal specimens of human ANCA-associated vasculitis. The current study aimed to investigate the clinical and pathologic significance of complement activation products in the urine and kidneys of patients with ANCA-associated vasculitis.
  
  
  METHODS
  Renal biopsy specimens from 29 patients with ANCA-associated vasculitis diagnosed at Peking University First Hospital from January of 2008 to December of 2010 were randomly collected. Urine samples from 27 of 29 patients in active stage and 22 ANCA-associated vasculitis patients in complete remission who were independent of the above-mentioned 29 patients were collected. Urine samples from 28 patients with lupus nephritis and 25 healthy individuals were also collected. The renal deposition of Bb, C3d, and C5b-9 were detected by immunohistochemistry. The urinary levels of Bb, C3a, C5a, and soluble C5b-9 were determined by ELISA.
  
  
  RESULTS
  The deposition, measured by the mean optical density of Bb, which is an alternative complement pathway marker, in glomeruli correlated with the proportion of total crescents (r=0.50, P=0.006), the extent of interstitial infiltrate (r=0.59, P=0.001), interstitial fibrosis (r=0.45, P=0.01), and tubular atrophy (r=0.55, P=0.002), whereas it correlated inversely with the proportion of normal glomeruli (r=-0.49, P=0.008). The urinary levels of Bb, C3a, C5a, and soluble C5b-9 were all significantly higher in active compared with remission stage. The urinary levels of Bb in patients with active ANCA-associated vasculitis correlated with the serum creatinine (r=0.56, P=0.002) and correlated inversely with the proportion of normal glomeruli in renal specimens (r=-0.49, P=0.009).
  
  
  CONCLUSIONS
  The present study provides additional evidence that complement activation through the alternative pathway occurred in the development of ANCA-associated vasculitis. The renal deposition of Bb and urinary Bb levels were associated with the severity of renal injury.
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Shen-Ju
authors.initials: SJ
authors.lastname: Gou
authors.forename: Jun
authors.initials: J
authors.lastname: Yuan
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Zhao
authors.forename: Min
authors.initials: M
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000652:urine*; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001706:Biopsy; D016022:Case-Control Studies; D002681:China; D011415:Complement Factor B / Q000652:urine; D003170:Complement Pathway, Alternative; D003165:Complement System Proteins / Q000652:urine*; D003404:Creatinine / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005921:Glomerulonephritis / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000652:urine*; D006785:Hospitals, University; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016482:Urinalysis / Q000379:methods; D055815:Young Adult
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; D003165:Complement System Proteins; D003404:Creatinine; D011415:Complement Factor B