title: Epitope analysis of myeloperoxidase (MPO) specific anti-neutrophil cytoplasmic autoantibodies (ANCA) in MPO-ANCA-associated glomerulonephritis.
abstract: OBJECTIVE
  Epitope analysis of sera from 20 patients with myeloperoxidase anti-neutrophil cytoplasmic antibody- (MPO-ANCA) associated glomerulonephritis was examined by Western blotting using a panel set of recombinant deletion mutants of MPO. Sera from 19 patients reacted with recombinants of MPO heavy chain, whereas no serum reacted with the light chain regions. The high frequency sites were regions on the upstream of Met341 (Ha region), on the upstream of Met409 (Hb region) near the N-terminus of the MPO heavy chain and a region on the downstream of Gly598 (Hg region) near the C-terminus. The epitope recognition profiles were classified into 2 groups. Group A, which had 1 or 2 regions in Ha, Hb and Hg, and group B, which had all 3 regions.
  
  
  RESULTS
  Incidence of alveolar hemorrhage (AH) and pulmonary fibrosis (PF) in group A was significantly higher than that in group B (AH: group A 9 of 13 (69.2%), group B 1 of 6 (16.7%) p < 0.05, PF: group A 10 of 13 (76.9%), group B 1 of 6 (16.7%) p < 0.05, AH and/or PH: group A 12 of 13 (92.3%) and group B 1 of 6 (16.7%) p < 0.01). Relapse rate for patients in the inactive stage in group A was significantly higher than that in group B (p < 0.05). T-cell reacted regions were Ha, Hb, Hg and the light chain of MPO recombinant fragments. Higher frequency of HLA typing with MHC class II DR9 was observed.
  
  
  CONCLUSIONS
  These results indicate that MPO-ANCA recognizes the linear site of the heavy chain of the MPO molecule. The epitope recognition profiles are related to the clinical features, suggesting the pathogenesis of MPO-ANCA-associated glomerulonephritis.
authors.affiliation: Department of Bioactive Molecules, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Fujii
authors.forename: K
authors.initials: K
authors.lastname: Tomizawa
authors.forename: Y
authors.initials: Y
authors.lastname: Arimura
authors.forename: T
authors.initials: T
authors.lastname: Nagasawa
authors.forename: Y Y
authors.initials: YY
authors.lastname: Ohashi
authors.forename: T
authors.initials: T
authors.lastname: Hiyama
authors.forename: S
authors.initials: S
authors.lastname: Mizuno
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D018604:Epitope Mapping; D005260:Female; D005921:Glomerulonephritis / Q000097:blood / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000276:immunology*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D009195:Peroxidase