title: Increased complement C4d deposition at the maternal-fetal interface in unexplained recurrent miscarriage.
abstract: C4d is a footprint of antibody-mediated classical complement activation, and has evolved as a useful diagnostic marker of antibody-mediated rejection. It is unknown if complement activation, as reflected by C4d deposition plays a role in unexplained recurrent miscarriage. In a case-control study products of conception of 35 women with three or more unexplained consecutive miscarriages within 20 weeks of gestation with the same partner (case group), 22 women with one spontaneous sporadic miscarriage and no history of complicated pregnancy(ies) (control group 1), and 40 women who underwent an elective abortion for psychosocial reasons (control group 2) were included. Immunohistochemical staining for C4d was performed on products of conception. Positivity for C4d was scored semi-quantitatively. C4d deposition was present in products of conception of 14 out of 35 women with unexplained recurrent miscarriage (40.0%), compared to 6 out of 22 women with a sporadic miscarriage (27.3%), and 4 out of 40 women with an elective abortion (10.0%) (p=0.020). C4d is increased at the maternal-fetal interface in women with unexplained recurrent miscarriage, which may reflect an aberrant anti-fetal immunity in these women. Further knowledge of the specific pathogenic mechanism may lead to the development of new treatment strategies for this group of women.
authors.affiliation: Department of Obstetrics, Leiden University Medical Center, 2300 RC Leiden, the Netherlands; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, the Netherlands. Electronic address: t.meuleman@lumc.nl.
authors.forename: Tess
authors.initials: T
authors.lastname: Meuleman
authors.affiliation: Department of Pathology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
authors.forename: Danielle
authors.initials: D
authors.lastname: Cohen
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
authors.forename: Godelieve M J S
authors.initials: GM
authors.lastname: Swings
authors.affiliation: Department of Pathology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Veraar
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.affiliation: Department of Obstetrics, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
authors.forename: Kitty W M
authors.initials: KW
authors.lastname: Bloemenkamp
mesh_terms: D000026:Abortion, Habitual / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D003181:Complement C4 / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D010920:Placenta / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy
chemical_list: D003181:Complement C4
keywords: C4d; Classical complement system; Recurrent miscarriage