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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 (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 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 Jozsi, M. Articles by Zipfel, P. F Search for Related Content PubMed PubMed Citation Articles by Jozsi, M. Articles by Zipfel, P. F Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 1, 2007 Accepted April 17, 2007 Anti-factor H autoantibodies block C-terminal recognition function of factor H in hemolytic uremic syndrome Mihaly Jozsi*, Stefanie Strobel, Hans-Martin Dahse, Wei-shih Liu, Peter F Hoyer, Martin Oppermann, Christine Skerka, and Peter F Zipfel Junior Research Group Cellular Immunobiology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany Department of Pediatric Nephrology, University Clinic Essen, University Duisburg-Essen, Essen, Germany Department of Cellular and Molecular Immunology, University of Gottingen, Gottingen, Germany Friedrich Schiller University, Jena, Germany * Corresponding author; email: mihaly.jozsi{at}hki-jena.de. 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 site of FH-autoantibodies from five unrelated aHUS patients were mapped using recombinant FH fragments and competitor antibodies. For all five 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 patient's plasma caused enhanced hemolysis of sheep erythrocytes, which was reversed by adding FH in excess. These results suggest that aHUS-associated FH-autoantibodies mimick 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. 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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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