Variations in glycosylation of von Willebrand factor with O-linked sialylated T antigen are associated with its plasma levels.

Abstract

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(alpha2-3)Gal-(beta1-3)-[NeuAc(alpha2-6)]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.

• Authors: Carina J M van Schooten, Cécile V Denis, Ton Lisman, Jeroen C J Eikenboom, Frank W Leebeek, Jenny Goudemand, Edith Fressinaud, H Marijke van den Berg, Philip G de Groot, Peter J Lenting
• Journal: Blood (Blood) Vol. 109 Issue 6 Pg. 2430-7 (Mar 15 2007) ISSN: 0006-4971 [Print] United States
• PMID: 17090649 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Viral, Tumor
• Peanut Agglutinin
• von Willebrand Factor
• N-Acetylneuraminic Acid

Topics

• Antigens, Viral, Tumor (blood, genetics)
• Genetic Variation (genetics)
• Glycosylation
• Humans
• Liver Cirrhosis (blood, genetics)
• N-Acetylneuraminic Acid (metabolism)
• Peanut Agglutinin (metabolism)
• Protein Binding
• Protein Processing, Post-Translational
• von Willebrand Factor (chemistry, genetics, metabolism)