title: AC13, a C-terminal fragment of apolipoprotein A-I, is a candidate biomarker for microscopic polyangiitis.
abstract: OBJECTIVE
  Microscopic polyangiitis (MPA) is necrotizing vasculitis of unknown etiology. We analyzed the serum peptide profile of MPA to find a biomarker for this disease.
  
  
  METHODS
  Serum peptides from 33 patients with MPA, 7 with granulomatosis with polyangiitis (Wegener's), 7 with Churg-Strauss syndrome, 6 with giant cell arteritis, and 25 with systemic lupus erythematosus (SLE) were comprehensively analyzed by mass spectrometry. Peptide function on human microvascular endothelial cells (HMVECs) was examined by enzyme-linked immunosorbent assay and real-time polymerase chain reaction.
  
  
  RESULTS
  A total of 102 serum peptides were detected from the 78 patients. One of the peptides, peptide 1,523, showed significantly higher ion intensity in MPA (mean ± SD 46.8 ± 39.3 arbitrary units [AU]) than in the other systemic vasculitides (14.1 ± 12.2 AU) (P < 0.05) or in SLE (17.0 ± 12.1 AU) (P < 0.05). In MPA, peptide 1,523 showed significantly higher ion intensity before treatment than 1 week (P < 0.05) and 6 weeks (P < 0.05) after the initiation of treatment. Peptide 1,523 was identified as 13 C-terminal amino acid residues of apolipoprotein A-I (Apo A-I) and was designated "AC13." Validation of AC13 ion intensity using another MPA cohort (n = 14) similarly showed significantly higher ion intensity (90.1 ± 167.9 AU) compared to 14 patients with rheumatoid arthritis (8.6 ± 5.4 AU) (P < 0.01) and 14 healthy subjects (11.8 ± 6.1 AU) (P < 0.01). Serum concentrations of Apo A-I and high-density lipoprotein cholesterol were down-regulated in MPA before treatment and returned to their normal ranges 6 weeks after the initiation of treatment (both P < 0.01). Stimulation of HMVECs with AC13 significantly up-regulated secretion of interleukin-6 (IL-6) (P < 0.05) and IL-8 (P < 0.01).
  
  
  CONCLUSIONS
  AC13, a candidate biomarker for MPA, may be useful for monitoring disease activity and may exacerbate vascular inflammation through up-regulation of proinflammatory cytokines.
authors.affiliation: St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Takakuwa
authors.forename: Manae S
authors.initials: MS
authors.lastname: Kurokawa
authors.forename: Seido
authors.initials: S
authors.lastname: Ooka
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sato
authors.forename: Kouhei
authors.initials: K
authors.lastname: Nagai
authors.forename: Mitsumi
authors.initials: M
authors.lastname: Arito
authors.forename: Naoya
authors.initials: N
authors.lastname: Suematsu
authors.forename: Kazuki
authors.initials: K
authors.lastname: Okamoto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nagafuchi
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Yamada
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ozaki
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kato
mesh_terms: D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood*; D015415:Biomarkers; D015267:Churg-Strauss Syndrome / Q000097:blood; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000097:blood; D006801:Humans; D008297:Male; D055953:Microscopic Polyangiitis / Q000097:blood*; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*
chemical_list: D016632:Apolipoprotein A-I; D015415:Biomarkers; D010446:Peptide Fragments