Eculizumab treatment during pregnancy does not affect the complement system activity of the newborn.
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.
['Hallstensen|Randi Fykse|RF|', 'Bergseth|Grethe|G|', 'Foss|Stian|S|', 'Jæger|Steinar|S|', 'Gedde-Dahl|Tobias|T|', 'Holt|Jan|J|', 'Christiansen|Dorte|D|', 'Lau|Corinna|C|', 'Brekke|Ole-Lars|OL|', 'Armstrong|Elina|E|', 'Stefanovic|Vedran|V|', 'Andersen|Jan Terje|JT|', 'Sandlie|Inger|I|', 'Mollnes|Tom Eirik|TE|']
D061067:Antibodies, Monoclonal, Humanized D000936:Antigen-Antibody Complex D016022:Case-Control Studies D003167:Complement Activation D003182:Complement C5 D003165:Complement System Proteins D005260:Female D006457:Hemoglobinuria, Paroxysmal D015395:Histocompatibility Antigens Class I D006801:Humans D007231:Infant, Newborn D018811:Maternal Exposure D011247:Pregnancy D011485:Protein Binding D011961:Receptors, Fc
Eculizumab Complement Paroxysmal nocturnal hemoglobinuria Placenta Therapy