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Lysosomal-associated membrane protein-2 plays an important role in the pathogenesis of primary cutaneous vasculitis.
MedLine Citation:
PMID:  23704322     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Sora Takeuchi; Satoko Kimura; Yoshinao Soma; Masashi Waki; Madoka Yamaguchi; Daigo Nakazawa; Utano Tomaru; Akihiro Ishizu; Tamihiro Kawakami
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-5-23
Journal Detail:
Title:  Rheumatology (Oxford, England)     Volume:  -     ISSN:  1462-0332     ISO Abbreviation:  Rheumatology (Oxford)     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-5-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100883501     Medline TA:  Rheumatology (Oxford)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Dermatology, St Marianna University School of Medicine, Kawasaki, Graduate School of Health Sciences, Hokkaido University, Sapporo, Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo and Faculty of Health Sciences, Hokkaido University, Sapporo, Japan.
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