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This Article Full Text (PDF) 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 De La Cadena, R. A. Articles by Colman, R. W. Search for Related Content PubMed PubMed Citation Articles by De La Cadena, R. A. Articles by Colman, R. W. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Naturally occurring human antibodies against two distinct functional domains in the heavy chain of FXI/FXIa RA De La Cadena, FA Baglia, CA Johnson, RE Wenk, R Amernick, PN Walsh and RW Colman Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA 19140. We have isolated and probed the mechanism of action of two naturally occurring antibodies (Baltimore and Winston-Salem) against factor XI (FXI), that developed in patients congenitally deficient in FXI after replacement therapy. Purification on immobilized protein A and neutralization with monospecific antibodies against IgG heavy and light chain subtypes indicated that both antibodies were of restricted heterogeneity. Both Winston-Salem (IgG3 kappa) and Baltimore (IgG1 kappa) completely inhibited FXI coagulant activity at titers of 200 and 8 Bethesda units, respectively. Immunoaffinity columns prepared from each antibody were able to bind the heavy but not the light chain of reduced and alkylated activated FXI (FXIa). The activation of purified FXI by activated bovine factor XII (FXIIa), a reaction independent of high molecular weight kininogen (HK), was not inhibited by either antibody. The active site on the FXIa light chain was unaffected by either patient's IgG, as measured by its amidolytic activity. In contrast, one antibody (Baltimore) or its Fab' blocked the surface- mediated proteolytic activation of FXI by human FXIIa in a concentration-dependent fashion by preventing its binding to HK, but had no effect on the rate of activation of FIX by FXIa. In contrast, the other antibody (Winston-Salem) or its Fab' inhibited the activation of FIX by FXIa in a concentration-dependent fashion but did not inhibit binding of FXI to HK. We conclude that each of these two naturally occurring antibodies is directed against a specific, separate, and distinct epitope located in the heavy chain of FXIa, one near or at the domain essential for the activation of FIX by FXIa and the other close to the domain required for binding to HK. Volume 72, Issue 5, pp. 1748-1754, 11/01/1988 Copyright © 1988 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: O. Salomon, A. Zivelin, T. Livnat, R. Dardik, R. Loewenthal, O. Avishai, D. M. Steinberg, M. H. Rosove, N. O'Connell, C. A. Lee, et al. Prevalence, causes, and characterization of factor XI inhibitors in patients with inherited factor XI deficiency Blood, June 15, 2003; 101(12): 4783 - 4788. [Abstract] [Full Text] [PDF]

	Copyright © 1988 by American Society of Hematology         Online ISSN: 1528-0020