Lysosomal-associated membrane protein-2 plays an important role in the pathogenesis of primary cutaneous vasculitis

Rheumatology (Oxford). 2013 Sep;52(9):1592-8. doi: 10.1093/rheumatology/ket159. Epub 2013 May 23.

Abstract

Objectives: 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.

Conclusion: These data support a positive relationship between anti-LAMP-2 antibody and cutaneous vasculitis.

Keywords: Henoch–Schönlein purpura; cutaneous polyarteritis nodosa; cutaneous vasculitis; lysosomal-associated membrane protein-2.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Autoantibodies / blood*
  • Female
  • Humans
  • IgA Vasculitis / blood*
  • IgA Vasculitis / immunology
  • IgA Vasculitis / pathology
  • Lysosomal-Associated Membrane Protein 2 / blood*
  • Lysosomal-Associated Membrane Protein 2 / immunology*
  • Male
  • Middle Aged
  • Polyarteritis Nodosa / blood*
  • Polyarteritis Nodosa / immunology
  • Polyarteritis Nodosa / pathology
  • Rats
  • Rats, Transgenic
  • Skin / metabolism*
  • Skin / pathology

Substances

  • Autoantibodies
  • Lysosomal-Associated Membrane Protein 2