• Animal models of antineutrophil cytoplasm antibody-associated vasculitis.

      Salama, Alan D; Little, Mark A; UCL Centre for Nephrology Royal Free Hospital, London, UK. a.salama@ucl.ac.uk (2012-01)
      To provide an update on the experimental models that have been developed recapitulating clinical antineutrophil cytoplasm antibody (ANCA) associated vasculitis. The application of the models in the study of pathogenesis, and the therapeutic implications of this, are covered in the article by van Timmeren and Heeringa in this issue.
    • Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles.

      Hong, Ying; Eleftheriou, Despina; Hussain, Abdullah A K; Price-Kuehne, Fiona E; Savage, Caroline O; Jayne, David; Little, Mark A; Salama, Alan D; Klein, Nigel J; Brogan, Paul A; et al. (2012-01)
      The mechanisms by which anti-neutrophil cytoplasmic antibodies (ANCAs) may contribute to the pathogenesis of ANCA-associated vasculitis are not well understood. In this study, both polyclonal ANCAs isolated from patients and chimeric proteinase 3-ANCA induced the release of neutrophil microparticles from primed neutrophils. These microparticles expressed a variety of markers, including the ANCA autoantigens proteinase 3 and myeloperoxidase. They bound endothelial cells via a CD18-mediated mechanism and induced an increase in endothelial intercellular adhesion molecule-1 expression, production of endothelial reactive oxygen species, and release of endothelial IL-6 and IL-8. Removal of the neutrophil microparticles by filtration or inhibition of reactive oxygen species production with antioxidants abolished microparticle-mediated endothelial activation. In addition, these microparticles promoted the generation of thrombin. In vivo, we detected more neutrophil microparticles in the plasma of children with ANCA-associated vasculitis compared with that in healthy controls or those with inactive vasculitis. Taken together, these results support a role for neutrophil microparticles in the pathogenesis of ANCA-associated vasculitis, potentially providing a target for future therapeutics.
    • Genetically distinct subsets within ANCA-associated vasculitis.

      Lyons, Paul A; Rayner, Tim F; Trivedi, Sapna; Holle, Julia U; Watts, Richard A; Jayne, David R W; Baslund, Bo; Brenchley, Paul; Bruchfeld, Annette; Chaudhry, Afzal N; et al. (The New England journal of medicine, 2012-07-19)
      Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis.
    • Renal transplantation in systemic vasculitis: when is it safe?

      Little, Mark A; Hassan, Basma; Jacques, Steve; Game, David; Salisbury, Emma; Courtney, Aisling E; Brown, Catherine; Salama, Alan D; Harper, Lorraine; Renal Institute of Birmingham, School of Immunity, Infection and Inflammation, University of Birmingham, Birmingham, UK. (Nephrology, dialysis, transplantation : official publication of the European, 2009-10)
      There are no clear guidelines on renal transplantation in patients with antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis.