| Literature DB >> 18836458 |
Renate Kain1, Markus Exner, Ricarda Brandes, Reinhard Ziebermayr, Dawn Cunningham, Carol A Alderson, Agnes Davidovits, Ingrid Raab, Renate Jahn, Oliver Ashour, Susanne Spitzauer, Gere Sunder-Plassmann, Minoru Fukuda, Per Klemm, Andrew J Rees, Dontscho Kerjaschki.
Abstract
Pauci-immune focal necrotizing glomerulonephritis (FNGN) is a severe inflammatory disease associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA). Here we characterize autoantibodies to lysosomal membrane protein-2 (LAMP-2) and show that they are a new ANCA subtype present in almost all individuals with FNGN. Consequently, its prevalence is nearly twice that of the classical ANCAs that recognize myeloperoxidase or proteinase-3. Furthermore, antibodies to LAMP-2 cause pauci-immune FNGN when injected into rats, and a monoclonal antibody to human LAMP-2 (H4B4) induces apoptosis of human microvascular endothelium in vitro. The autoantibodies in individuals with pauci-immune FNGN commonly recognize a human LAMP-2 epitope (designated P(41-49)) with 100% homology to the bacterial adhesin FimH, with which they cross-react. Rats immunized with FimH develop pauci-immune FNGN and also develop antibodies to rat and human LAMP-2. Finally, we show that infections with fimbriated pathogens are common before the onset of FNGN. Thus, FimH-triggered autoimmunity to LAMP-2 provides a previously undescribed clinically relevant molecular mechanism for the development of pauci-immune FNGN.Entities:
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Year: 2008 PMID： 18836458 PMCID： PMC2751601 DOI： 10.1038/nm.1874
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440