title: Eculizumab treatment during pregnancy does not affect the complement system activity of the newborn.
abstract: Eculizumab is a humanized IgG2/4 chimeric anti-complement C5 antibody used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) or atypical hemolytic uremic syndrome. The aim of this study was to evaluate whether or not the complement activity in newborns from pregnant women who receive eculizumab is impaired. A novel eculizumab-C5 complex (E-C5) specific assay was developed and revealed that two newborns carried only 6-7% of the E-C5 detected in their eculizumab-treated PNH mothers. Serum from the pregnant women completely lacked terminal complement pathway activity, whereas the complement activity in the serum of the newborns was completely normal. Data from the pregnant women and their newborns were compared with that of healthy age-matched female controls and healthy newborns, as well as a non-treated pregnant woman with PNH and her newborn. These all showed normal complement activity without detectable E-C5 complexes. Furthermore, absence of eculizumab or E-C5 in the newborn could not be explained by lack of eculizumab binding to the neonatal Fc receptor (FcRn), as eculizumab bound strongly to the receptor in vitro. In conclusion, despite binding to FcRn neither eculizumab nor E-C5 accumulates in fetal plasma, and eculizumab treatment during pregnancy does not impair the complement function in the newborn.
authors.affiliation: Division of Internal Medicine, Nordland Hospital, Bodø, Norway.
authors.forename: Randi Fykse
authors.initials: RF
authors.lastname: Hallstensen
authors.affiliation: Research Laboratory, Nordland Hospital, Bodø, Norway.
authors.forename: Grethe
authors.initials: G
authors.lastname: Bergseth
authors.affiliation: Centre for Immune Regulation, University of Oslo, Norway; Department of Immunology, Oslo University Hospital Rikshospitalet and University of Oslo, Norway; Department of Biosciences, University of Oslo, Norway.
authors.forename: Stian
authors.initials: S
authors.lastname: Foss
authors.affiliation: Division of Internal Medicine, Nordland Hospital, Bodø, Norway.
authors.forename: Steinar
authors.initials: S
authors.lastname: Jæger
authors.affiliation: Department of Hematology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Tobias
authors.initials: T
authors.lastname: Gedde-Dahl
authors.affiliation: Division of Pediatrics, Nordland Hospital, Bodø, Norway.
authors.forename: Jan
authors.initials: J
authors.lastname: Holt
authors.affiliation: Research Laboratory, Nordland Hospital, Bodø, Norway.
authors.forename: Dorte
authors.initials: D
authors.lastname: Christiansen
authors.affiliation: Research Laboratory, Nordland Hospital, Bodø, Norway.
authors.forename: Corinna
authors.initials: C
authors.lastname: Lau
authors.affiliation: Research Laboratory, Nordland Hospital, Bodø, Norway; Faculty of Health Sciences, University of Tromsø, Norway.
authors.forename: Ole-Lars
authors.initials: OL
authors.lastname: Brekke
authors.affiliation: Coagulation Disorder Unit, Department of Hematology, Helsinki University Central Hospital Comprehensive Cancer Center, Helsinki, Finland.
authors.forename: Elina
authors.initials: E
authors.lastname: Armstrong
authors.affiliation: Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Vedran
authors.initials: V
authors.lastname: Stefanovic
authors.affiliation: Centre for Immune Regulation, University of Oslo, Norway; Department of Immunology, Oslo University Hospital Rikshospitalet and University of Oslo, Norway.
authors.forename: Jan Terje
authors.initials: JT
authors.lastname: Andersen
authors.affiliation: Centre for Immune Regulation, University of Oslo, Norway; Department of Immunology, Oslo University Hospital Rikshospitalet and University of Oslo, Norway; Department of Biosciences, University of Oslo, Norway.
authors.forename: Inger
authors.initials: I
authors.lastname: Sandlie
authors.affiliation: Research Laboratory, Nordland Hospital, Bodø, Norway; Department of Immunology, Oslo University Hospital Rikshospitalet and University of Oslo, Norway; Faculty of Health Sciences, University of Tromsø, Norway; Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address: t.e.mollnes@medisin.uio.no.
authors.forename: Tom Eirik
authors.initials: TE
authors.lastname: Mollnes
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D000936:Antigen-Antibody Complex / Q000097:blood / Q000276:immunology; D016022:Case-Control Studies; D003167:Complement Activation / Q000187:drug effects*; D003182:Complement C5 / Q000037:antagonists & inhibitors / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D005260:Female; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D018811:Maternal Exposure; D011247:Pregnancy; D011485:Protein Binding / Q000276:immunology; D011961:Receptors, Fc / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000936:Antigen-Antibody Complex; D003182:Complement C5; D015395:Histocompatibility Antigens Class I; D011961:Receptors, Fc; D003165:Complement System Proteins; C481642:eculizumab; C100688:Fc receptor, neonatal
keywords: Complement; Eculizumab; Paroxysmal nocturnal hemoglobinuria; Placenta; Therapy