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Blood, 15 September 2004, Vol. 104, No. 6, pp. 1711-1715. Prepublished online as a Blood First Edition Paper on May 27, 2004; DOI 10.1182/blood-2004-02-0462. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-02-0462v1 104/6/1711    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 Lieby, P. Articles by Pasquali, J.-L. Search for Related Content PubMed PubMed Citation Articles by Lieby, P. Articles by Pasquali, J.-L. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Pathogenic antiphospholipid antibody: an antigen-selected needle in a haystack Patricia Lieby, Vincent Poindron, Stamatiki Roussi, Cyril Klein, Anne-Marie Knapp, Jean-Claude Garaud, Martine Cerutti, Thierry Martin, and Jean-Louis Pasquali From the Laboratoire d'Immunopathologie, Institut National de la Santé etdela Recherche Medicale, Equipe Mixte Inserum (INSERM EMI) 0222, Institut d'Immunohématologie, Hôpital central, Hôpitaux Universitaires de Strasbourg, France; and Institute National de la Recherche Agronomique—Centre National de la Recherche Scientifique—Unité Mixte de Recherche (INRA-CNRS-UMR) 5087, Laboratoire de pathologie comparée, 30380 St Christol les Ales, France. Antiphospholipid antibodies represent a heterogeneous group of autoantibodies directed against anionic phospholipids (PLs) usually linked to protein cofactors. Their presence during the antiphospholipid syndrome is associated with risks of thrombosis and fetal losses. Among 5 randomly selected monoclonal antiphospholipid antibodies, all originating from a single patient suffering from this autoimmune disease, only 1 induced fetal losses when passively injected into pregnant mice. Its antiphospholipid activity was dependent on annexin A5, and its variable regions contained mainly 3 replacement mutations. To clarify the role of these mutations in the pathogenicity of the antibody, they were in vitro reverted to the germ line configuration. The resulting "germ line" antibody reacted with multiple self-antigens and only partially lost its reactivity against PLs, but it was no more dependent on annexin A5 and, more importantly, was no more pathogenic. This study illustrates that the in vivo antigen-driven maturation process of natural autoreactive B cells can be responsible for pathogenicity. (Blood. 2004;104:1711-1715) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Giles, N. Lambrianides, N. Pattni, D. Faulkes, D. Latchman, P. Chen, S. Pierangeli, D. Isenberg, and A. Rahman Arginine Residues Are Important in Determining the Binding of Human Monoclonal Antiphospholipid Antibodies to Clinically Relevant Antigens J. Immunol., August 1, 2006; 177(3): 1729 - 1736. [Abstract] [Full Text] [PDF] S. Yurasov, H. Wardemann, J. Hammersen, M. Tsuiji, E. Meffre, V. Pascual, and M. C. Nussenzweig Defective B cell tolerance checkpoints in systemic lupus erythematosus J. Exp. Med., March 7, 2005; 201(5): 703 - 711. [Abstract] [Full Text] [PDF]

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