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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2430-2437. Prepublished online as a Blood First Edition Paper on November 7, 2006; DOI 10.1182/blood-2006-06-032706. This Article Full Text (PDF) All Versions of this Article: blood-2006-06-032706v1 109/6/2430    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 van Schooten, C. J. Articles by Lenting, P. J. Search for Related Content PubMed PubMed Citation Articles by van Schooten, C. J. Articles by Lenting, P. J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 29, 2006 Accepted November 1, 2006 Variations in glycosylation of von Willebrand factor with O-linked sialylated T-antigen are associated with its plasma levels Carina JM van Schooten, Cecile V Denis, Ton Lisman, Jeroen CJ Eikenboom, Frank W Leebeek, Jenny Goudemand, Edith Fressinaud, Marijke van den Berg, Philip G de Groot, and Peter J. Lenting* University Medical Center Utrecht, Netherlands Universite Paris-Sud, France Leiden University Medical Center, Netherlands Erasmus University Medical Center, Netherlands Medical University of Lille, Hopital Cardiogique, France Centre Hospitalier Universitaire, France * Corresponding author; email: p.j.lenting{at}umcutrecht.nl. The glycosylation-profile of von Willebrand factor (VWF) is known to strongly influence its plasma levels. VWF contains several carbohydrate structures, including O-linked glycans that primarily consist of sialylated T-antigen (NeuAc(2-3)Gal-(1-3)-[NeuAc(2-6)]GalNAc). It is unknown yet if O-linked carbohydrates affect VWF levels. We developed an immunosorbent-assay based on neuraminidase-incubation allowing subsequent binding of Peanut-Agglutinin (PNA) to de-sialylated O-linked T-antigen on VWF. An inverse relation was found between PNA-binding and VWF-antigen levels in healthy individuals (n=111; Pearson-rank=-0.43; p<0.0001). A similar inverse association was observed in randomly-selected plasma-samples from our diagnostic laboratory: 252±125% for VWF<0.5 U/ml (n=15); 131±36% for VWF between 0.5 and 1.5 U/ml (n=32); 92±40% for VWF>1.5 U/ml (n=19). Reduced or increased PNA-binding was also observed in patients with increased (liver cirrhosis) or reduced (von Willebrand disease (VWD)-type 1) VWF-antigen levels, respectively. VWD-type 1 patients further displayed increased ratios of propeptide over mature VWF-antigen levels (0.38±0.18 versus 0.17±0.03 for patients and controls, respectively; p<0.0001), which is indicative for reduced VWF survival in these patients. Interestingly, a linear relation between PNA-binding and propeptide/VWF ratio was observed (Spearman-rank=0.47), suggesting a potential association between O-linked glycosylation and VWF survival. Finally, we detected a marked decrease in PNA-binding in post-DDAVP samples from various patients, indicating that the O-linked glycosylation profile of VWF stored in endothelial storage-organelles may differ from circulating VWF. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Gallinaro, M. G. Cattini, M. Sztukowska, R. Padrini, F. Sartorello, E. Pontara, A. Bertomoro, V. Daidone, A. Pagnan, and A. Casonato A shorter von Willebrand factor survival in O blood group subjects explains how ABO determinants influence plasma von Willebrand factor Blood, April 1, 2008; 111(7): 3540 - 3545. [Abstract] [Full Text] [PDF]

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