SEARCH:   Advanced

Blood, 1 June 2008, Vol. 111, No. 11, pp. 5307-5315. Prepublished online as a Blood First Edition Paper on February 11, 2008; DOI 10.1182/blood-2007-08-106153. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-08-106153v1 111/11/5307    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 CrossRef Google Scholar Articles by Ståhl, A.-l. Articles by Karpman, D. PubMed PubMed Citation Articles by Ståhl, A.-l. Articles by Karpman, D. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Factor H dysfunction in patients with atypical hemolytic uremic syndrome contributes to complement deposition on platelets and their activation Anne-lie Ståhl1, Fariba Vaziri-Sani1, Stefan Heinen2, Ann-Charlotte Kristoffersson1, Karl-Henrik Gydell3, Reem Raafat4, Alberto Gutierrez5, Ortraud Beringer6, Peter F. Zipfel2,7, and Diana Karpman1 1 Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden; 2 Department of Biological Infection, Hans Knoell Institute for Natural Products Research, Jena, Germany; 3 Department of Internal Medicine, Regional Hospital, Halmstad, Sweden; 4 Department of Pediatric Nephrology, University of Texas Health Science Center at San Antonio, TX; 5 Division of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden; 6 Children's University Hospital, Tübingen, Germany; and 7 Friedrich Schiller University, Jena, Germany Atypical hemolytic uremic syndrome (aHUS) may be associated with mutations in the C-terminal of factor H (FH). FH binds to platelets via the C-terminal as previously shown using a construct consisting of short consensus repeats (SCRs) 15 to 20. A total of 4 FH mutations, in SCR15 (C870R) and SCR20 (V1168E, E1198K, and E1198Stop) in patients with aHUS, were studied regarding their ability to allow complement activation on platelet surfaces. Purified FH-E1198Stop mutant exhibited reduced binding to normal washed platelets compared with normal FH, detected by flow cytometry. Washed platelets taken from the 4 patients with aHUS during remission exhibited C3 and C9 deposition, as well as CD40-ligand (CD40L) expression indicating platelet activation. Combining patient serum/plasma with normal washed platelets led to C3 and C9 deposition, CD40L and CD62P expression, aggregate formation, and generation of tissue factor-expressing microparticles. Complement deposition and platelet activation were reduced when normal FH was preincubated with platelets and were minimal when using normal serum. The purified FH-E1198Stop mutant added to FH-deficient plasma (complemented with C3) allowed considerable C3 deposition on washed platelets, in comparison to normal FH. In summary, mutated FH enables complement activation on the surface of platelets and their activation, which may contribute to the development of thrombocytopenia in aHUS. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Unleashed platelets in aHUS Vahid Afshar-Kharghan Blood 2008 111: 5266. [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020