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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 5, 2004 Accepted April 27, 2004 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* Laboratoire d'Immunopathologie, INSERM EMI 0222, Strasbourg, France Laboratoire de pathologie comparee, INRA-CNRS-UMR5087, St Christol les Ales, France * Corresponding author; email: Jean-Louis.Pasquali{at}hemato-ulp.u-strasbg.fr. Antiphospholipid antibodies represent a heterogeneous group of autoantibodies directed against anionic phospholipids (PL) 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 one 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 germline configuration. The resulting "germline" antibody reacted with multiple self-antigens, only partially lost its reactivity against PL, but 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Giles, C. Pericleous, X. Liu, J. Ehsanullah, L. Clarke, P. Brogan, M. Newton-West, R. Swerlick, A. Lambrianides, P. Chen, et al. Thrombin Binding Predicts the Effects of Sequence Changes in a Human Monoclonal Antiphospholipid Antibody on Its In Vivo Biologic Actions J. Immunol., April 15, 2009; 182(8): 4836 - 4843. [Abstract] [Full Text] [PDF] I Giles, A Lambrianides, and A Rahman Examining the non-linear relationship between monoclonal antiphospholipid antibody sequence, structure and function Lupus, October 1, 2008; 17(10): 895 - 903. [Abstract] [PDF] 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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