title: Lysosomal-associated membrane protein-2 plays an important role in the pathogenesis of primary cutaneous vasculitis.
abstract: OBJECTIVE
  Recent research suggests that lysosomal-associated membrane protein-2 (LAMP-2) could be one of the target antigens in the pathogenesis of vasculitides. We established a transgenic rat model, env-pX rats, with various vasculitides including cutaneous vasculitis. Human primary cutaneous vasculitis includes cutaneous polyarteritis nodosa (CPN) and Henoch-Schönlein purpura (HSP). We measured serum anti-LAMP-2 antibody levels in morbid env-pX rats and injected anti-LAMP-2 antibody into premorbid env-pX rats. We further measured serum anti-LAMP-2 antibody levels in patients with CPN and HSP.
  
  
  METHODS
  Cutaneous vasculitis was observed in ∼30% of 6-month-old morbid env-pX rats. In contrast, these findings were rare in premorbid env-pX rats under 3 months old. We also examined 85 patients with CPN and 36 adult patients with HSP. Serum anti-LAMP-2 antibody levels were determined using ELISA. Premorbid env-pX rats under 3 months old were given an i.v. injection of anti-LAMP-2 antibody at day 0 and day 7. At day 14, these rats underwent histopathological and direct immunofluorescence examination. Cell surface LAMP-2 expression of rat neutrophils was examined by flow cytometry.
  
  
  RESULTS
  Serum anti-LAMP-2 antibody levels were significantly higher in morbid env-pX rats than in wild-type normal rats. In addition, the levels in the cutaneous vasculitis group of morbid env-pX rats were significantly higher than the no cutaneous vasculitis group. Intravenous anti-LAMP-2 antibody injection into premorbid env-pX rats under 3 months old induced infiltration of neutrophils into cutaneous small vessels. Anti-LAMP-2 antibody-binding neutrophils were detected there. LAMP-2 expression on the cell surface of neutrophils in premorbid env-pX rats under PMA stimulation was higher compared with controls. Serum anti-LAMP-2 antibody levels in CPN and HSP were significantly higher than those of healthy controls.
  
  
  CONCLUSIONS
  These data support a positive relationship between anti-LAMP-2 antibody and cutaneous vasculitis.
authors.affiliation: Department of Dermatology, St Marianna University School of Medicine, Miyamae-ku, Kawasaki, Kanagawa, Japan.
authors.forename: Sora
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Satoko
authors.initials: S
authors.lastname: Kimura
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Soma
authors.forename: Masashi
authors.initials: M
authors.lastname: Waki
authors.forename: Madoka
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Daigo
authors.initials: D
authors.lastname: Nakazawa
authors.forename: Utano
authors.initials: U
authors.lastname: Tomaru
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ishizu
authors.forename: Tamihiro
authors.initials: T
authors.lastname: Kawakami
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D006801:Humans; D011695:IgA Vasculitis / Q000097:blood* / Q000276:immunology / Q000473:pathology; D052119:Lysosomal-Associated Membrane Protein 2 / Q000097:blood* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010488:Polyarteritis Nodosa / Q000097:blood* / Q000276:immunology / Q000473:pathology; D051381:Rats; D055647:Rats, Transgenic; D012867:Skin / Q000378:metabolism* / Q000473:pathology
chemical_list: D001323:Autoantibodies; D052119:Lysosomal-Associated Membrane Protein 2
keywords: Henoch–Schönlein purpura; cutaneous polyarteritis nodosa; cutaneous vasculitis; lysosomal-associated membrane protein-2