title: Effect of maternal anti-HPA-1a antibodies and polyclonal IVIG on the activation status of vascular endothelial cells.
abstract: Maternal anti-HPA-1a antibodies can cause severe fetal and neonatal alloimmune thrombocytopenia (FNAIT), complicated by intracranial haemorrhage (ICH). Antenatal treatment with maternal intravenous immunoglobulin (IVIG) seems to protect against ICH even when thrombocytopenia persists. The aim of this study was to investigate if anti-HPA-1a antibodies and IVIG potentially affect vascular endothelial cells (ECs) in order to identify susceptibility for ICH. Human umbilical cord endothelial cells (HUVEC) were incubated with anti-HPA-1a antibodies with or without polyclonal IVIG and evaluated for EC activation. Maternal sera with anti-HPA-1a antibodies affected neither the EC expression of intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and tissue factor (TF) nor the release of van Willebrand factor (vWF) or interleukin (IL)-8 nor the integrity of ECs. Maternal sera obtained after IVIG treatment and polyclonal IVIG decrease constitutive and cytokine-induced ICAM-1 and VCAM-1 expression on ECs. The results show that maternal anti-HPA-1a antibodies cause no activation or damage of ECs in this model. The clinical relevance of the de-activating properties of IVIG on EC activation with respect to ICH deserves further investigation.
authors.affiliation: Department of Obstetrics, Leiden University Medical Centre, Leiden, The Netherlands. C.M.Radder@LUMC.nl
authors.forename: C M
authors.initials: CM
authors.lastname: Radder
authors.forename: H
authors.initials: H
authors.lastname: Beekhuizen
authors.forename: H H H
authors.initials: HH
authors.lastname: Kanhai
authors.forename: A
authors.initials: A
authors.lastname: Brand
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D016824:Antigens, Human Platelet / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology*; D007231:Infant, Newborn; D039661:Integrin beta3; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007371:Interferon-gamma / Q000276:immunology; D016209:Interleukin-8 / Q000032:analysis; D020300:Intracranial Hemorrhages / Q000276:immunology / Q000517:prevention & control; D008431:Maternal-Fetal Exchange / Q000276:immunology; D011247:Pregnancy; D013925:Thromboplastin / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D000888:Antibodies, Anti-Idiotypic; D016824:Antigens, Human Platelet; C061248:ITGB3 protein, human; D016756:Immunoglobulins, Intravenous; D039661:Integrin beta3; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D013925:Thromboplastin