Pathogenesis of ANCA-Associated Vasculitis

@article{CartinCeba2012PathogenesisOA,
  title={Pathogenesis of ANCA-Associated Vasculitis},
  author={Rodrigo Cartin-Ceba and Tobias D. Peikert and Ulrich Specks},
  journal={Current Rheumatology Reports},
  year={2012},
  volume={14},
  pages={481-493}
}
Antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitides (AAV) are a group of systemic vasculitis syndromes characterized by inflammation and necrosis of blood vessel walls. Genetic, epigenetic, and environmental factors contribute to the etiology and pathogenesis of AAV. On the basis of currently available clinical and experimental evidence, it is reasonable to believe that, in predisposed patients, different triggers can lead to the production of autoantibodies (ANCA) that, in… 
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References

SHOWING 1-10 OF 175 REFERENCES
Netting neutrophils in autoimmune small-vessel vasculitis
TLDR
It is shown that chromatin fibers, so-called neutrophil extracellular traps (NETs), are released by ANCA-stimulated neutrophils and contain the targeted autoantigens proteinase-3 and myeloperoxidase (MPO).
Genetically distinct subsets within ANCA-associated vasculitis.
TLDR
This study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyang iitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature ofproteinase 3 ANCA -associated vasulitis.
Review article: The role of CD4+ T cells in ANCA‐associated systemic vasculitis
TLDR
Future perspectives for treatment of AASV could be built on neutralization of IL‐17 and depletion of CD4+ TEM cells, which could suggest involvement of cell‐mediated injury in this disorder.
Immunogenetic risk factors for anti‐neutrophil cytoplasmic antibody (ANCA)‐associated systemic vasculitis
TLDR
Several haplotypes on chromosome 6p appeared strongly associated with proteinase 3 (PR3)‐ANCA+ AASV, as in other autoimmune diseases, different predisposing factors play differential aetiopathogenic roles in various groups of AASv patients.
Are there specific genetic risk factors for the different forms of ANCA-associated vasculitis?
TLDR
Several clinical and histopathological features unique to one disease (eg, asthma for CSS) support Hoffman's opinion, and analysis of the genetic background of the three disorders may help to differentiate between both concepts.
Increased levels of BLyS and sVCAM-1 in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitides (AAV).
TLDR
Enhanced levels of sVCAM-1 represent a marker for endothelial cell activation in AAV and might indicate the influence of the vasculitic process on renal function.
Pulmonary-renal syndrome in a newborn with placental transmission of ANCAs.
TLDR
The case of a woman with a history of pulmonary-renal syndrome caused by MPA whose disease became clinically and serologically active during pregnancy is described, representing the first human model supporting the interpretation that MPO-ANCAs were immunopathogenic.
Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice.
TLDR
This animal model offers strong support for a direct pathogenic role for ANCA IgG in human glomerulonephritis and vasculitis as well as the pathogenic potential of antibodies alone.
Antineutrophil cytoplasmic autoantibodies against the murine homolog of proteinase 3 (Wegener autoantigen) are pathogenic in vivo.
TLDR
This in vivo study provides the first evidence for a pathogenic effect of proteinase 3-specific ANCAs at local sites of inflammation.
Antineutrophil cytoplasm antibodies directed against myeloperoxidase augment leukocyte-microvascular interactions in vivo.
TLDR
This study provides the first direct in vivo evidence for the ability of ANCAs to enhance leukocyte-endothelial interactions and cause microvascular hemorrhage, thereby providing a mechanism by which ANCAs could exert pathogenic effects in systemic vasculitis.
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