title: Epitope analysis of myeloperoxidase-specific antineutrophil cytoplasmic autoantibodies (MPO-ANCA) in childhood onset Graves' disease treated with propylthiouracil.
abstract: OBJECTIVE
  This study aimed to elucidate the relationship between epitope profiles and clinical manifestations of patients with myeloperoxidase antineutrophil cytoplasmic autoantibodies-(MPO-ANCA) positive childhood onset Graves' disease treated with propylthiouracil (PTU).
  
  
  METHODS
  Sixteen patients were studied. The patients were grouped into ten without clinical vasculitis and nephritis (non-vasculitis group) and six with biopsy-proven pauci-immune necrotizing crescentic glomerulonephritis (vasculitis group). Epitope analysis was performed on serum samples by an enzyme-linked immunosorbent assay (ELISA) using a panel of recombinant deletion mutants of MPO.
  
  
  RESULTS
  The high frequency sites were region upstream of Met341 (Ha region) near the N-terminus of the heavy chain, and regions downstream of Gly598 (Hf and Hg regions) near the C-terminus. Most patients in the non-vasculitis group had polyclonal MPO-ANCA recognizing both the above linear sites and other epitope sites of the heavy chain of MPO. Only one of ten patients in the non-vasculitis group, and four of six patients in the vasculitis group had MPO-ANCA recognizing only the linear sites of the heavy chain of the MPO molecule (Ha, Hf and/or Hg). Of the four patients in the vasculitis group, two had nephritis, like rapidly progressive glomerulonephritis and one had alveolar hemorrhage.
  
  
  CONCLUSIONS
  These findings suggest that most patients with childhood onset Graves' disease treated with PTU who manifest no vasculitis have polyclonal MPO-ANCA recognizing both the linear and other epitope sites of the heavy chain of MPO. However, some patients who develop nephritis have MPO-ANCA recognizing only the linear sites of the heavy chain of MPO. This clonality of MPO-ANCA may be a risk factor that induces clinical vasculitis and nephritis in patients treated with PTU. Therefore, patients exposed to PTU should be monitored for MPO-ANCA level and epitopes.
authors.affiliation: Department of Pediatrics, Kochi University Medical School, Kochi, Japan. fujiedam@med.kochi-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Fujieda
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: M
authors.initials: M
authors.lastname: Hattori
authors.forename: N
authors.initials: N
authors.lastname: Wada
authors.forename: M
authors.initials: M
authors.lastname: Tsuchiya
authors.forename: N
authors.initials: N
authors.lastname: Okamoto
authors.forename: T
authors.initials: T
authors.lastname: Murata
authors.forename: M
authors.initials: M
authors.lastname: Matsudaira
authors.forename: M
authors.initials: M
authors.lastname: Shimizu
authors.forename: K
authors.initials: K
authors.lastname: Ohta
authors.forename: K
authors.initials: K
authors.lastname: Naruse
authors.forename: S
authors.initials: S
authors.lastname: Sugihara
authors.forename: H
authors.initials: H
authors.lastname: Wakiguchi
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood / Q000276:immunology*; D015415:Biomarkers; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes / Q000032:analysis*; D005260:Female; D006111:Graves Disease / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D006801:Humans; D008297:Male; D009195:Peroxidase / Q000097:blood / Q000276:immunology*; D015995:Prevalence; D012720:Severity of Illness Index
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; D000939:Epitopes; D009195:Peroxidase