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This Article Full Text Full Text (PDF) Erratum (v97,p1542) 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 Nogami, K. Articles by Yoshioka, A. Search for Related Content PubMed PubMed Citation Articles by Nogami, K. Articles by Yoshioka, A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 February 2001, Vol. 97, No. 3, pp. 669-677 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Circulating factor VIII immune complexes in patients with type 2 acquired hemophilia A and protection from activated protein C-mediated proteolysis Keiji Nogami, Midori Shima, John C. Giddings, Kazuya Hosokawa, Masanori Nagata, Seiki Kamisue, Hiroshi Suzuki, Masaru Shibata, Evgueni L. Saenko, Ichiro Tanaka, and Akira Yoshioka From the Department of Pediatrics, Nara Medical University, Kashihara City, Nara, Japan; Department of Haematology, University of Wales College of Medicine, Cardiff, United Kingdom; Fujimori Kogyo Co, Kawasaki City, Kanagawa, Japan; and American Red Cross, Holland Laboratory, Rockville, Maryland. Factor VIII (FVIII) inhibitor antibodies are classified into 2 groups according to the kinetic pattern of FVIII inactivation. Type 2 antibodies are more commonly observed in patients with acquired hemophilia A and do not completely inhibit FVIII activity; in most cases, substantial levels of circulating FVIII are detected. Three type 2 autoantibodies from patients who had normal levels of FVIII antigen despite having low levels of FVIII activity were studied. The antibodies reacted exclusively with the light chain of FVIII but not with the C2 domain, and their epitopes were therefore ascribed to the regions in the A3-C1 domains. Heavy and light chains of FVIII were detected in plasma-derived immune complexes extracted by using protein G Sepharose. Direct binding assays using anhydro-activated protein C (anhydro-APC), a catalytically inactive derivative of activated protein C (APC) in which the active-site serine is converted to dehydroalanine, were used to examine the relation between immune complexes and APC. The intact FVIII, 80-kd light chain, and 72-kd light chain bound in a dose-dependent manner to anhydro-APC, with Kd values of 580, 540, and 310 nM, respectively, whereas no appreciable binding was detected for the heavy chain. The 3 autoantibodies blocked FVIII binding to anhydro-APC by approximately 80% and consequently inhibited APC-induced FVIII proteolytic inactivation. These antibodies also bound to a synthetic peptide, His2009-Val2018, which contains the APC binding site. The findings suggest that binding of type 2 autoantibodies, recognizing residues His2009 to Val2018, protects FVIII from APC-mediated proteolysis and might contribute to the presence of FVIII immune complexes in the circulation. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Nogami, M. Shima, K. Nishiya, K. Hosokawa, E. L. Saenko, Y. Sakurai, M. Shibata, H. Suzuki, I. Tanaka, and A. Yoshioka A novel mechanism of factor VIII protection by von Willebrand factor from activated protein C-catalyzed inactivation Blood, May 13, 2002; 99(11): 3993 - 3998. [Abstract] [Full Text] [PDF]

	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020