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Background: Henoch-Schönlein purpura (HSP) is an lgA mediated small vessel systemic vasculitis disease in children. The etiology and pathogenesis of HSP disease remain unknown. However, environmental and genetic risk factors could play important roles in susceptibility to HSP disease. In this study we investigated the association of 5՛-untranslated region polymorphism (-634G/C) of VEGF gene with HSP among Iranian Azeri Turkish population. Methods: Thirty unrelated Iranian Azeri Turkish children with HSP and fifty healthy unrelated subjects without HSP and other inflammatory diseases were enrolled in this population. -634G/C polymorphism of VEGF gene was genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) technique. Results: The distribution of CC genotype in VEGF -634G/C polymorphism statistically showed a significant difference in HSP patients in compare to that of control group (P= 0.009). Conclusions: The CC genotype of VEGF -634G/C polymorphism could be associated with susceptibility to HSP disease in Iranian Azeri Turkish ethnic group.

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Regarding the importance of inhibiting VEGF and unique features of VHHs as a new generation of antibody-based therapeutics, the present study aimed to generate VHHs against the receptor binding domain of VEGF, thereby blocking of VEGF binding to its receptor. After preparing the gene repertoire of VHH fragments from an immunized camel, a VHH phage display library was constructed. We adopted a stringent successive biopanning to isolate the phages displaying VHH with high affinity to VEGF-RBD.A significant enrichment of phages that specifically bound to the target protein was obtained after six rounds of panning. Of the specific clones with high binding affinity screened by monoclonal phage ELISA, 52% shared the same VHH sequence, showing its high enrichment. Using molecular simulation of antigen-antibody interaction based on the crystallographic information of VEGF/VEGFR2, molecular dynamics simulations and MM/PBSA free energy calculations, we provide a reliable picture of the binding site of antibody on antigen. The key residues in the VEvhh1-VEGF interface were dissected and the energetics was analyzed by MM/PBSA. The results of studies revealed that VEvhh1 binds to the receptor binding site of VEGF with high binding energy and showed the highest affinity to the residues of VEGF which are responsible for VEGF binding to VEGFR2. Also the antibody potently covers these key functional residues of VEGF, thereby inhibiting VEGF binding to its receptor and probably abrogating its biological activity. This study may represent VEvhh1 as an anti-VEGF and anti-angiogenic candidate.