SEARCH:   Advanced

Blood, 15 May 2007, Vol. 109, No. 10, pp. 4376-4382. Prepublished online as a Blood First Edition Paper on January 30, 2007; DOI 10.1182/blood-2005-12-019604. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2005-12-019604v1 109/10/4376    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jarius, S. Articles by Voltz, R. Search for Related Content PubMed PubMed Citation Articles by Jarius, S. Articles by Voltz, R. Related Collections Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Intravenous immunoglobulins contain naturally occurring antibodies that mimic antineutrophil cytoplasmic antibodies and activate neutrophils in a TNF-dependent and Fc-receptor–independent way Sven Jarius1,2, Peter Eichhorn3, Michael H. Albert4, Stefan Wagenpfeil5, Manfred Wick3, Bernd H. Belohradsky4, Reinhard Hohlfeld1,2, Dieter E. Jenne2, and Raymond Voltz1,2,6 1 Institute of Clinical Neuroimmunology, Ludwig Maximilians University, Munich, Germany; 2 Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, Germany; 3 Institute of Clinical Chemistry, Ludwig Maximilians University, Munich, Germany; 4 Dr v. Haunersches Kinderspital, Ludwig Maximilians University, Munich, Germany; 5 Institute of Medical Statistics and Epidemiology, Technical University, Munich, Germany; 6 Department of Palliative Medicine, University of Cologne, Cologne, Germany Intravenous immunoglobulin (IVIg) preparations are increasingly used for therapy of several neuroimmunologic diseases. IVIg therapy is considered safe, although serious side effects like aseptic meningitis, cerebral vasospasm, or ischemic encephalopathy have been reported. These side effects are frequently associated with neutrophilic pleocytosis in the cerebrospinal fluid (CSF), suggesting a neutrophil-mediated mechanism. To elucidate the potential role of neutrophil activation, we analyzed IVIg preparations from 5 different commercial sources for the presence of antineutrophil cytoplasmic antibody (ANCA)–like immunoglobulins against ethanol-fixed peripheral-blood neutrophils, purified human antigens, and a panel of human and nonhuman tissues. All IVIg batches tested (n = 13) contained atypical ANCAs (IgG titer up to 1:2048, IgA up to 1:512). Moreover, all preparations were capable of inducing hydrogen peroxide production in TNF-primed human neutrophils, with a significant correlation (P < .005) between atypical ANCA titers in IVIg preparations and neutrophil activation. Fc-mediated binding and activation was ruled out by the use of IVIg-F(ab')2 fragments. Our findings strongly suggest that in vivo activation of TNF-primed neutrophils by atypical ANCAs of IVIg may contribute to the side effects of IVIg therapy and for the first time demonstrate that the activation of neutrophil granulocytes by IVIg occurs in an Fc receptor (FcR)–independent, hence antigen-dependent, way. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020