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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4514-4519. Prepublished online as a Blood First Edition Paper on March 4, 2004February 19, 2004; DOI 10.1182/blood-2003-12-4165. This Article Full Text (PDF) All Versions of this Article: 2003-12-4165v1 2003-12-4165v2 103/12/4514    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 Klaus, C. Articles by Scheiflinger, F. Search for Related Content PubMed PubMed Citation Articles by Klaus, C. Articles by Scheiflinger, F. Social Bookmarking                   What's this? Submitted December 9, 2003 Accepted January 31, 2004 Epitope mapping of ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura Christoph Klaus, Barbara Plaimauer, Jan-Dirk Studt, Friedrich Dorner, Bernhard Laemmle, Pier M Mannucci, and Friedrich Scheiflinger* Preclinical Product Development, Baxter BioScience, Orth, Austria Central Hematology Laboratory, University Hospital Bern, Bern, Switzerland Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, Milan, Kyrgyzstan * Corresponding author; email: scheiff{at}baxter.com. A severe deficiency of the von Willebrand factor (VWF)-cleaving protease, ADAMTS13, can lead to thrombotic thrombocytopenic purpura (TTP), a disease associated with the widespread formation of platelet-rich thrombi in many organs. Autoantibodies that inactivate ADAMTS13 are the most frequent cause of acquired TTP. Little is known about epitope specificity and reactivity of anti-ADAMTS13 antibodies. In this study a series of ADAMTS13 domains were expressed in Escherichia coli and the reactivity of purified recombinant fragments with anti-ADAMTS13 autoantibodies from 25 patients with severe ADAMTS13 deficiency was evaluated in vitro. All TTP plasmas contained antibodies directed against the cysteine-rich and the spacer domain (cys-rich/spacer) of ADAMTS13. In the plasmas of 3 patients antibodies were detected that reacted exclusively with the cys-rich/spacer domain, underscoring the importance of this region for functional activity of ADAMTS13. In 64% of the plasmas antibodies reacted with the two cub domains and in 56% with the isolated first thrombospondin type 1 repeat (TSP-1) and with the compound fragment consisting of the catalytic, the disintegrin-like and the TSP1-1 domain. Less frequent, in 28%, antibodies reacted with the TSP1 repeats 2-8. Unexpectedly, antibodies reacted with the propeptide region in 20% of the plasmas. This study shows that even though anti-ADAMTS13 autoantibodies react with multiple domains of the protease, the cys-rich/spacer domain is consistently involved in antibody reactivity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Akiyama, S. Takeda, K. Kokame, J. Takagi, and T. Miyata Crystal structures of the noncatalytic domains of ADAMTS13 reveal multiple discontinuous exosites for von Willebrand factor PNAS, November 17, 2009; 106(46): 19274 - 19279. [Abstract] [Full Text] [PDF] M. Galbusera, M. Noris, and G. Remuzzi Inherited thrombotic thrombocytopenic purpura Haematologica, February 1, 2009; 94(2): 166 - 170. [Full Text] [PDF] J. E. Sadler Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura Blood, July 1, 2008; 112(1): 11 - 18. [Abstract] [Full Text] [PDF] B. Lammle, J. A. Kremer Hovinga, and J. N. 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