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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.
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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Variations in glycosylation of von Willebrand factor with O-linked sialylated T antigen are associated with its plasma levels
Carina J. M. van Schooten1,
Cécile V. Denis2,
Ton Lisman1,
Jeroen C. J. Eikenboom3,
Frank W. Leebeek4,
Jenny Goudemand5,
Edith Fressinaud6,
H. Marijke van den Berg1,7,
Philip G. de Groot1, and
Peter J. Lenting1
1 Laboratory for Thrombosis and Haemostasis, Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, the Netherlands;
2 Institut National de la Santé et de la Recherche Médicale U770, Le Kremlin-Bicêtre, France; Univ Paris-Sud, Université Paris-Sud 11, Le Kremlin-Bicêtre, France;
3 Department of Haematology, Haemostasis and Thrombosis Research Center, Leiden University Medical Center, Leiden, the Netherlands;
4 Department of Haematology, Erasmus University Medical Center, Rotterdam, the Netherlands;
5 Department of Haematology, Medical University of Lille, Hôpital Cardiologique, Lille, France;
6 Centre d'Exploration Biologique des Maladies Hémorragiques et Thrombotiques, Centre Hospitalier Universitaire, Nantes, France;
7 Van Creveldkliniek, University Medical Center Utrecht, Utrecht, the Netherlands
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-(ß1-3)-[NeuAc(2-6)]GalNAc). It is not yet known whether O-linked carbohydrates affect VWF levels. We developed an immunosorbent assay based on neuraminidase incubation allowing subsequent binding of peanut agglutinin (PNA) to desialylated 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 < .001). A similar inverse association was observed in randomly selected plasma samples from our diagnostic laboratory: 252% ± 125% for VWF levels less than 0.5 U/mL (n = 15); 131% ± 36% for VWF levels between 0.5 and 1.5 U/mL (n = 32); and 92% ± 40% for VWF levels more than 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 < .001), which is indicative of reduced VWF survival in these patients. Of interest, 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 (1-deamino-8-D-arginine vasopressin) samples from various patients, indicating that the O-linked glycosylation profile of VWF stored in endothelial storage organelles may differ from circulating VWF.
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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.
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