Journal
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Volume 169, Issue 3, Pages 229-237Publisher
WILEY
DOI: 10.1111/j.1365-2249.2012.04616.x
Keywords
antibody; model; mouse; neutrophil; vasculitis
Categories
Funding
- Kidney Research UK
- Sir Jules Thorn Charitable Trust
- Genzyme Renal Innovations Program
- Guys and St Thomas' Kidney Patients Association
- Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre
- King's College London
- King's College Hospital NHS Foundation Trust
- MRC Centre for Transplantation
- Kidney Research UK [RP15/2009] Funding Source: researchfish
- Medical Research Council [MR/J006742/1] Funding Source: researchfish
Ask authors/readers for more resources
OTHER ARTICLES PUBLISHED ON ANCA IN THIS ISSUE How anti-neutrophil cytoplasmic autoantibodies activate neutrophils. Clinical and Experimental Immunology 2012, 169: 2208. Summary Antibodies against neutrophil proteins myeloperoxidase (MPO) and proteinase 3 are thought to cause disease in anti-neutrophil cytoplasmic antibody (ANCA) vasculitis. There have been a number of recent developments in the animal models of ANCA vasculitis in both mice and rats. These include models based on an immune response to MPO generated in MPO-deficient mice, with other models using MPO-sufficient mice and rats. In addition, there is a report of the use of humanized mice where immunodeficient mice have been engrafted with human haematopoietic stem cells and injected with patient ANCA. Antibodies to another protein lysosomal-associated protein-2 have been found in patients with ANCA vasculitis, and evidence from a rat model suggests that they are also pathogenic. These models all have advantages and disadvantages, which are discussed. We also consider what these models have taught us about the pathogenesis of ANCA vasculitis. Experiments using genetically modified mice and pharmacological inhibition have given insights into disease mechanisms and have identified potential therapeutic targets. Toll-like receptor stimulation modifies disease by acting both at the level of tissue injury and in the generation of the autoimmune response. Complement is also potentially important with data to support the role of the alternative pathway and C5a in particular. Intracellular pathways have been examined, with a role showing p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase ?. Serine proteases are now known to contribute to disease by release of interleukin-1 beta in ANCA-activated neutrophils and monocytes. Other potential therapies studied in these models include the use of bortezemib and strategies to modify antibody glycosylation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available