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Blood, 1 September 2007, Vol. 110, No. 5, pp. 1516-1518. Prepublished online as a Blood First Edition Paper on May 10, 2007; DOI 10.1182/blood-2007-02-071472. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-02-071472v1 110/5/1516    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 Józsi, M. Articles by Zipfel, P. F. Search for Related Content PubMed PubMed Citation Articles by Józsi, M. Articles by Zipfel, P. F. Related Collections Hemostasis, Thrombosis, and Vascular Biology Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Brief Report Anti–factor H autoantibodies block C-terminal recognition function of factor H in hemolytic uremic syndrome Mihály Józsi1, Stefanie Strobel1, Hans-Martin Dahse2, Wei-shih Liu3, Peter F. Hoyer3, Martin Oppermann4, Christine Skerka2, and Peter F. Zipfel2,5 1 Junior Research Group Cellular Immunobiology and 2 Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena; 3 Department of Pediatric Nephrology, University Clinic Essen, University Duisburg-Essen, Essen; 4 Department of Cellular and Molecular Immunology, University of Göttingen, Göttingen; and 5 Friedrich Schiller University, Jena, Germany The atypical form of the kidney disease hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. In addition to mutations in complement regulators, factor H (FH)–specific autoantibodies have been reported for aHUS patients. The aim of the present study was to understand the role of these autoantibodies in aHUS. First, the binding sites of FH autoantibodies from 5 unrelated aHUS patients were mapped using recombinant FH fragments and competitor antibodies. For all 5 autoantibodies, the binding site was localized to the FH C-terminus. In a functional assay, isolated patient IgG inhibited FH binding to C3b. In addition, autoantibody-positive patients' plasma caused enhanced hemolysis of sheep erythrocytes, which was reversed by adding FH in excess. These results suggest that aHUS-associated FH autoantibodies mimic the effect of C-terminal FH mutations, as they inhibit the regulatory function of FH at cell surfaces by blocking its C-terminal recognition region. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Abarrategui-Garrido, R. Martinez-Barricarte, M. Lopez-Trascasa, S. Rodriguez de Cordoba, and P. Sanchez-Corral Characterization of complement factor H-related (CFHR) proteins in plasma reveals novel genetic variations of CFHR1 associated with atypical hemolytic uremic syndrome Blood, November 5, 2009; 114(19): 4261 - 4271. [Abstract] [Full Text] [PDF] M. Noris and G. Remuzzi Atypical Hemolytic-Uremic Syndrome N. Engl. J. Med., October 22, 2009; 361(17): 1676 - 1687. [Full Text] [PDF] S. Heinen, A. Hartmann, N. Lauer, U. Wiehl, H.-M. Dahse, S. Schirmer, K. Gropp, T. Enghardt, R. Wallich, S. Halbich, et al. Factor H-related protein 1 (CFHR-1) inhibits complement C5 convertase activity and terminal complex formation Blood, September 17, 2009; 114(12): 2439 - 2447. [Abstract] [Full Text] [PDF] T. Kwon, A. Belot, B. Ranchin, V. Baudouin, V. Fremeaux-Bacchi, M.-A. Dragon-Durey, P. Cochat, and C. Loirat Varicella as a trigger of atypical haemolytic uraemic syndrome associated with complement dysfunction: two cases Nephrol. Dial. Transplant., September 1, 2009; 24(9): 2752 - 2754. [Abstract] [Full Text] [PDF] S. Strobel, P. F. Hoyer, C. J. Mache, E. Sulyok, W.-s. Liu, H. Richter, M. Oppermann, P. F. Zipfel, and M. Jozsi Functional analyses indicate a pathogenic role of factor H autoantibodies in atypical haemolytic uraemic syndrome Nephrol. Dial. Transplant., August 7, 2009; (2009) gfp388v1. [Abstract] [Full Text] [PDF] C. J. Mache, B. Acham-Roschitz, V. Fremeaux-Bacchi, M. Kirschfink, P. F. Zipfel, S. Roedl, U. Vester, and E. Ring Complement Inhibitor Eculizumab in Atypical Hemolytic Uremic Syndrome Clin. J. Am. Soc. Nephrol., August 1, 2009; 4(8): 1312 - 1316. [Abstract] [Full Text] [PDF] T. Kwon, M.-A. Dragon-Durey, M.-A. Macher, V. Baudouin, A. Maisin, M. Peuchmaur, V. Fremeaux-Bacchi, and C. Loirat Successful pre-transplant management of a patient with anti-factor H autoantibodies-associated haemolytic uraemic syndrome Nephrol. Dial. Transplant., June 1, 2008; 23(6): 2088 - 2090. [Full Text] [PDF] A.-l. Stahl, F. Vaziri-Sani, S. Heinen, A.-C. Kristoffersson, K.-H. Gydell, R. Raafat, A. Gutierrez, O. Beringer, P. F. Zipfel, and D. Karpman Factor H dysfunction in patients with atypical hemolytic uremic syndrome contributes to complement deposition on platelets and their activation Blood, June 1, 2008; 111(11): 5307 - 5315. [Abstract] [Full Text] [PDF] R. Martinez-Barricarte, G. Pianetti, R. Gautard, J. Misselwitz, L. Strain, V. Fremeaux-Bacchi, C. Skerka, P. F. Zipfel, T. Goodship, M. Noris, et al. The Complement Factor H R1210C Mutation Is Associated With Atypical Hemolytic Uremic Syndrome J. Am. Soc. Nephrol., March 1, 2008; 19(3): 639 - 646. [Abstract] [Full Text] [PDF] M. Jozsi, C. Licht, S. Strobel, S. L. H. Zipfel, H. Richter, S. Heinen, P. F. Zipfel, and C. Skerka Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency Blood, February 1, 2008; 111(3): 1512 - 1514. [Abstract] [Full Text] [PDF]

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