Glomerular deposition of myeloperoxidase and NETS in human ANCA associated vasculitis correlates with DTH effector cell accumulation

Abstract

Event Abstract Back to Event Glomerular deposition of myeloperoxidase and NETS in human ANCA associated vasculitis correlates with DTH effector cell accumulation Kim M. O'Sullivan1*, Sharon L. Ford1, Camden Lo2, Shaun A. Summers1, 3, A. R. Kitching1, 3 and Stephen R. Holdsworth1, 3 1 Monash University, Department of Medicine, Australia 2 Monash University, Monash Micro Imaging, Australia 3 Monash Medical Centre, Department of Nephrology, Australia Myeloperoxidase (MPO) autoimmunity underlies most cases of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis and glomerulonephritis. We sought evidence for the hypothesis that glomerular injury is initiated by ANCA induced neutrophil accumulation, degranulation and NET formation. This is substantially exacerbated by anti MPO CD4 T cells recognising extracellular MPO then directing DTH effector macrophages. Forty eight renal biopsies from ANCA MPO positive patients with clinically active glomerulonephritis were examined by confocal microscopy for leukocytes and MPO. A significant infiltration of MPO+CD15+ neutrophils and MPO+CD68+monocytes/macrophages was present in all biopsies. Significant correlation was found for simultaneous glomerular infiltration of CD4 T cells and MPO expressing cells (P<0.05), and simultaneous infiltration of CD15 and MPO positive cells, and CD68 and MPO positive cells ( P=0.004, P=0.035 respectively). Interstitial CD15 positive cells and the total number of MPO positive cells correlated inversely with estimated glomerular infiltration rate at time of biopsy and at 1 year (P<0.05 and, P<0.01, respectively.) Extracellular MPO was found in 93% of all glomeruli and made up 23% of the total proportion of MPO observed within glomeruli and 31% of all the MPO in the interstitium. Neutrophil extracellular traps (NETs) were present in 61.3% of MPO-ANCA biopsies and there was a significantly more CD15 cells, total MPO expression and extracellular MPO in the glomeruli of patients with the presence of NETs (P< 0.05). This study provides evidence to support the hypothesis that neutrophil derived extracellular MPO acts as a planted autoantigen in glomeruli inducing T cell mediated DTH type injury. Keywords: human ANCA vasculitis, Myeloperoxidase (MPO), Neutrophils, monocytes/macrophages, neutrophil extracellular traps (NETs), T cells Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: O'Sullivan KM, Ford SL, Lo C, Summers SA, Kitching AR and Holdsworth SR (2013). Glomerular deposition of myeloperoxidase and NETS in human ANCA associated vasculitis correlates with DTH effector cell accumulation. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00685 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Ms. Kim M O'Sullivan, Monash University, Department of Medicine, Melbourne, Victoria, 3134, Australia, kim.osullivan@monash.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Kim M O'Sullivan Sharon L Ford Camden Lo Shaun A Summers A. R Kitching Stephen R Holdsworth Google Kim M O'Sullivan Sharon L Ford Camden Lo Shaun A Summers A. R Kitching Stephen R Holdsworth Google Scholar Kim M O'Sullivan Sharon L Ford Camden Lo Shaun A Summers A. R Kitching Stephen R Holdsworth PubMed Kim M O'Sullivan Sharon L Ford Camden Lo Shaun A Summers A. R Kitching Stephen R Holdsworth Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.