%0 Journal Article
%T Antigenic Peptides Capable of Inducing Specific Antibodies for Detection of the Major Alterations Found in Type 2B Von Willebrand Disease
%A Marina de Oliveira Paro
%A Cyntia Silva Ferreira
%A Fernanda Silva Vieira
%A Marcos Aur¨¦lio de Santana
%A William Castro-Borges
%A Maria Sueli Silva Namen-Lopes
%A Sophie Yvette Leclercq
%A Cibele Velloso-Rodrigues
%A Milton H¨¦rcules Guerra de Andrade
%J International Journal of Peptides
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/590329
%X Von Willebrand disease (VWD) is an inherited hemorrhagic disorder promoted by either quantitative or qualitative defects of the von Willebrand factor (VWF). The disease represents the most common human coagulopathy afflicting 1.3% of the population. Qualitative defects are subdivided into four subtypes and classified according to the molecular dysfunction of the VWF. The differential diagnosis of the VWD is a difficult task, relying on a panel of tests aimed to assess the plasma levels and function of the VWF. Here, we propose biochemical approaches for the identification of structural variants of the VWF. A bioinformatic analysis was conducted to design seven peptides among which three were representatives of specific amino acid sequences belonging to normal VWF and four encompassed sequences found in the most common VWD subtype 2B. These peptides were used to immunize mice, after which, peptide-specific immunoglobulins were purified. This resulted in four Ig preparations capable of detecting alterations in the subtype 2B VWD plus additional three antibody fractions targeting the normal VWF. The panel of antibodies could serve many applications among them (1) assessment of VWF: antigen interaction, (2) VWF multimer analysis, and (3) production of monoclonal antibodies against VWF for therapeutic purposes as in thrombotic thrombocytopenic purpura. 1. Introduction Von Willebrand disease (VWD) is an inherited hemorrhagic disturbance related to quantitative and/or qualitative defects of the von Willebrand factor (VWF) [1, 2]. VWD prevalence varies between 0.8 and 2.0%, depending on the investigated population, being considered the most common coagulopathy afflicting humans [3]. The VWF is a multimeric plasma protein, composed of a varying number of 250£¿kDa monomers, which exhibits an essential role in primary haemostasis. Some of its reported functions are the attachment of platelets to subendothelial collagen at injured sites (platelet plug formation) and protection, binding, and transportation of coagulation factor VIII [4]. Mechanisms leading to the disease present themselves as highly diverse at the molecular level, giving rise to a variety of clinical outcomes. Through different laboratory criteria it is possible to identify three primary types of the disease [5]. Alterations on the plasma levels of VWF are associated with VWD types 1 and 3, whereas structural and functional defects of VWF result in VWD type 2 [3, 6¨C11]. VWD types 1 and 3 reflect, respectively, partial and complete deficiency of the VWF. VWD type 2 is also classified into four
%U http://www.hindawi.com/journals/ijpep/2013/590329/