Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis

作者：Kain Renate^*; Exner Markus; Brandes Ricarda; Ziebermayr Reinhard; Cunningham Dawn; Alderson Carol A; Davidovits Agnes; Raab Ingrid; Jahn Renate; Ashour Oliver; Spitzauer Susanne; Sunder Plassmann Gere; Fukuda Minoru; Klemm Per; Rees Andrew J; Kerjaschki Dontscho

来源：Nature Medicine, 2008, 14(10): 1088-1096.

DOI：10.1038/nm.1874

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 P41-49) with 100% homology to the bacterial adhesin FimH, with which they cross-react. Rats immunized with Ill 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.

• 出版日期2008-10
• 单位河北医科大学