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 (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 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 Citing Articles via Google Scholar Google Scholar Articles by Stahl, A.-l. Articles by Karpman, D. Search for Related Content PubMed PubMed Citation Articles by Stahl, A.-l. Articles by Karpman, D. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 8, 2007 Accepted February 7, 2008 Factor H dysfunction in patients with atypical hemolytic uremic syndrome contributes to complement deposition on platelets and their activation Anne-lie Stahl, Fariba Vaziri-Sani, Stefan Heinen, Ann-Charlotte Kristoffersson, Karl-Henrik Gydell, Reem Raafat, Alberto Gutierrez, Ortraud Beringer, Peter F. Zipfel, and Diana Karpman* Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden Department of Biological Infection, Hans Knoell Institute for Natural Products Research, Jena, Germany Department of Internal Medicine, Regional Hospital, Halmstad, Sweden Department of Pediatric Nephrology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States Division of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden Children's University Hospital, University of Tubingen, Tubingen, Germany Friedrich Schiller University, Jena, Germany * Corresponding author; email: diana.karpman{at}med.lu.se. Atypical hemolytic uremic syndrome (aHUS) may be associated with mutations at 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) 15-20. Four FH mutations, in SCR15 (C870R) and SCR20 (V1168E, E1198K, E1198Stop) in aHUS patients, were studied regarding their ability to allow complement activation on platelet surfaces. Purified FH-E1198Stop mutant exhibited reduced binding to normal washed platelets compared to normal FH, detected by flow cytometry. Washed platelets taken from the four aHUS patients 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 pre-incubated 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