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Blood, 1 September 2004, Vol. 104, No. 5, pp. 1411-1418. Prepublished online as a Blood First Edition Paper on May 18, 2004; DOI 10.1182/blood-2004-01-0267. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 2004-01-0267v1 104/5/1411    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pfister, H. Articles by Jenne, D. E. Search for Related Content PubMed PubMed Citation Articles by Pfister, H. Articles by Jenne, D. E. Related Collections Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Antineutrophil cytoplasmic autoantibodies against the murine homolog of proteinase 3 (Wegener autoantigen) are pathogenic in vivo Heiko Pfister, Markus Ollert, Leopold F. Fröhlich, Leticia Quintanilla-Martinez, Thomas V. Colby, Ulrich Specks, and Dieter E. Jenne From the Department of Neuroimmunology, Max-Planck Institute of Neurobiology, Martinsried, Germany; Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany; Division of Environmental Dermatology and Allergy, GSF-Research Center for Environment and Health, Neuherberg, Germany; Institute of Pathology, GSF-Research Center for Environment and Health, Neuherberg, Germany; Department of Pathology, Mayo Clinic, Scottsdale, AZ; and Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN. Antineutrophil cytoplasmic autoantibodies (ANCAs) recognizing human proteinase 3 of neutrophil granules are a diagnostic hallmark of Wegener granulomatosis, an autoimmune systemic vasculitis with predilection for the respiratory tract and kidneys. In vitro experiments have implicated several mechanisms by which ANCAs may lead to tissue injury. However, little is known about the pathogenic significance of proteinase 3–specific antibodies in vivo. In vivo models for ANCA-mediated proinflammatory effects have not been forthcoming, primarily because ANCA epitopes on human proteinase 3 are not shared by the murine homolog. In this study we generated ANCAs against recombinant murine proteinase 3 in proteinase 3/neutrophil elastase–deficient mice that recognized the murine antigen on the surface of neutrophils. Local inflammation induced by intradermal injection of tumor necrosis factor triggered a stronger subcutaneous panniculitis in the presence of passively transferred systemic proteinase 3–ANCAs than in the presence of mock immune serum. When we transferred mouse proteinase 3-ANCA serum to systemically lipopolysaccharide-primed wild-type mice, mice treated with proteinase 3-ANCAs did not develop significantly stronger signs of inflammation of the lungs or kidneys than the respective mock immune serum-treated animals. In conclusion, our in vivo study provides the first evidence for a pathogenic effect of proteinase 3–specific ANCAs at local sites of inflammation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C Mukhtyar, O Flossmann, B Hellmich, P Bacon, M Cid, J W Cohen-Tervaert, W L Gross, L Guillevin, D Jayne, A Mahr, et al. Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force Ann Rheum Dis, July 1, 2008; 67(7): 1004 - 1010. [Abstract] [Full Text] [PDF] Y. M van der Geld, T. Hellmark, D. Selga, P. Heeringa, M. G Huitema, P. C Limburg, and C. G M Kallenberg Rats and mice immunised with chimeric human/mouse proteinase 3 produce autoantibodies to mouse Pr3 and rat granulocytes Ann Rheum Dis, December 1, 2007; 66(12): 1679 - 1682. [Abstract] [Full Text] [PDF] S. von Vietinghoff, G. Tunnemann, C. Eulenberg, M. Wellner, M. Cristina Cardoso, F. C. Luft, and R. Kettritz NB1 mediates surface expression of the ANCA antigen proteinase 3 on human neutrophils Blood, May 15, 2007; 109(10): 4487 - 4493. [Abstract] [Full Text] [PDF] C. Kallenberg, C. Stegeman, H Bootsma, M Bijl, and P. Limburg Quantitation of Autoantibodies in Systemic Autoimmune Diseases: Clinically Useful? Lupus, July 1, 2006; 15(7): 397 - 402. [Abstract] [PDF] P M Aries, B Hellmich, J Voswinkel, M Both, B Nolle, K Holl-Ulrich, P Lamprecht, and W L Gross Lack of efficacy of rituximab in Wegener's granulomatosis with refractory granulomatous manifestations Ann Rheum Dis, July 1, 2006; 65(7): 853 - 858. [Abstract] [Full Text] [PDF] J Voswinkel, A Mueller, J A Kraemer, P Lamprecht, K Herlyn, K Holl-Ulrich, A C Feller, S Pitann, A Gause, and W L Gross B lymphocyte maturation in Wegener's granulomatosis: a comparative analysis of VH genes from endonasal lesions Ann Rheum Dis, July 1, 2006; 65(7): 859 - 864. [Abstract] [Full Text] [PDF] E. Csernok, M. Ai, W. L. Gross, D. Wicklein, A. Petersen, B. Lindner, P. Lamprecht, J. U. Holle, and B. Hellmich Wegener autoantigen induces maturation of dendritic cells and licenses them for Th1 priming via the protease-activated receptor-2 pathway Blood, June 1, 2006; 107(11): 4440 - 4448. [Abstract] [Full Text] [PDF] M. D. Morgan, L. Harper, J. Williams, and C. Savage Anti-Neutrophil Cytoplasm-Associated Glomerulonephritis J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1224 - 1234. [Abstract] [Full Text] [PDF] J. C. Jennette, H. Xiao, and R. J. Falk Pathogenesis of Vascular Inflammation by Anti-Neutrophil Cytoplasmic Antibodies J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1235 - 1242. [Abstract] [Full Text] [PDF] M. Feldmann and C. D. Pusey Is There a Role for TNF-{alpha} in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis? Lessons from Other Chronic Inflammatory Diseases J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1243 - 1252. [Abstract] [Full Text] [PDF] K. A. Keogh, S. R. Ytterberg, F. C. Fervenza, K. A. Carlson, D. R. Schroeder, and U. Specks Rituximab for Refractory Wegener's Granulomatosis: Report of a Prospective, Open-Label Pilot Trial Am. J. Respir. Crit. Care Med., January 15, 2006; 173(2): 180 - 187. [Abstract] [Full Text] [PDF] C Mukhtyar and R Luqmani Current state of tumour necrosis factor {alpha} blockade in Wegener's granulomatosis Ann Rheum Dis, November 1, 2005; 64(suppl_4): iv31 - iv36. [Abstract] [Full Text] [PDF] A. Schreiber, B. Otto, X. Ju, M. Zenke, U. Goebel, F. C. Luft, and R. Kettritz Membrane Proteinase 3 Expression in Patients with Wegener's Granulomatosis and in Human Hematopoietic Stem Cell-Derived Neutrophils J. Am. Soc. Nephrol., July 1, 2005; 16(7): 2216 - 2224. [Abstract] [Full Text] [PDF]

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