Shining a LAMP on pauci-immune focal segmental glomerulonephritis.
Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis frequently presents with renal involvement manifested by a focal segmental necrotizing glomerulonephritis, which is typically pauci-immune. Although considerable insight has been gained regarding potential mechanisms of organ damage, researchers have remained relatively ignorant of the initiating factors breaking immune tolerance. A recent report has provided evidence that molecular mimicry may be critical, with immune responsiveness toward a bacterial fimbrial protein inducing a cross-reactive autoimmune response toward lysosomal-associated membrane protein-2 (LAMP-2). Use of an experimental model demonstrates that this response generates ANCA and provokes pulmonary-renal disease, reminiscent of human ANCA-associated vasculitis. Greater understanding of the immune mechanisms underlying the development of ANCA should lead to more focused approaches to the treatment of small-vessel vasculitis.
Salama
Alan D
AD
Imperial College Kidney and Transplant Institute, Division of Medicine, Imperial College London, Hammersmith Hospital, London, UK. A.salama@imperial.ac.uk
Pusey
Charles D
CD
D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2 / Q000276:immunology*; D018448:Models, Immunological; D014657:Vasculitis / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D052119:Lysosomal-Associated Membrane Protein 2