Placental complement activation in fetal and neonatal alloimmune thrombocytopenia: An observational study
de Vos, Thijs W.; Winkelhorst, Dian; Baelde, Hans J.; Dijkstra, Kyra L.; van Bergen, Rianne D.M.; van der Meeren, Lotte E.; Nikkels, Peter G.J.; Porcelijn, Leendert; van der Schoot, C. Ellen; Vidarsson, Gestur; Eikmans, Michael; Kapur, Rick; van der Keur, Carin; Trouw, Leendert A.; Oepkes, Dick; Lopriore, Enrico; van der Hoorn, Marie Louise P.; Bos, Manon; de Haas, Masja
(2021) International journal of molecular sciences, volume 22, issue 13, pp. 1 - 11
(Article)
Abstract
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that causes thrombo-cytopenia and a risk of bleeding in the (unborn) child that result from maternal alloantibodies directed against fetal, paternally inherited, human platelet antigens (HPA). It is hypothesized that these alloantibodies can also bind to the placenta, causing placental damage.
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This study aims to explore signs of antibody-mediated placental damage in FNAIT. We performed a retrospective study that included pregnant women, their newborns, and placentas. It comprised 23 FNAIT cases, of which nine were newly diagnosed (14 samples) and 14 were antenatally treated with intravenous immune globulins (IVIg) (21 samples), and 20 controls, of which 10 had anti-HLA-class I antibodies. Clinical information was collected from medical records. Placental samples were stained for complement activation markers (C1q, C4d, SC5b-9, and mannose-binding lectin) using immunohistochemistry. Histopathology was examined according to the Amsterdam criteria. A higher degree of C4d deposition was present in the newly diagnosed FNAIT cases (10/14 samples), as compared to the IVIg-treated FNAIT cases (2/21 samples, p = 0.002) and anti-HLA-negative controls (3/20 samples, p = 0.006). A histopathological examination showed delayed maturation in four (44%) placentas in the newly diagnosed FNAIT cases, five (36%) in the IVIg-treated FNAIT cases, and one in the controls (NS). C4d deposition at the syncytiotrophoblast was present in combination with low-grade villitis of unknown etiology in three newly diagnosed FNAIT cases that were born SGA. We conclude that a higher degree of classical pathway-induced complement activation is present in placentas from pregnancies with untreated FNAIT. This may affect placental function and fetal growth.
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Keywords: Alloimmunization during pregnancy, Classical pathway complement activation, Fetal growth restriction, Fetal neonatal alloimmune thrombocytopenia, Histopathology placenta, Placental dysfunction, Fetus/immunology, Placenta/immunology, Humans, Histocompatibility Antigens Class I/immunology, Male, Case-Control Studies, Pregnancy, Complement Activation/immunology, Antibodies/immunology, Thrombocytopenia, Neonatal Alloimmune/immunology, Adult, Female, Immunoglobulins, Intravenous/immunology, Retrospective Studies, Infant, Newborn, fetal neonatal alloimmune thrombocytopenia, histopathology placenta, placental dysfunction, fetal growth restriction, classical pathway complement activation, alloimmunization during pregnancy, Molecular Biology, Spectroscopy, Catalysis, Inorganic Chemistry, Computer Science Applications, Physical and Theoretical Chemistry, Organic Chemistry, Journal Article
ISSN: 1661-6596
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
Note: Funding Information: Funded by Fonds Gezond Geboren (E50-03-LUMC) and Process and Product Development Diagnostic Services, Sanquin (SQI/00034).We want to thank the laboratory of platelet and leukocyte serology at Sanquin, Amsterdam that collected the cohort of newly diagnosed FNAIT samples. Also we would like to thank the department of Department of Immunogenetics, Sanquin, Amsterdam and the Department of Immunology at the Leiden University Medical Center, Leiden for performing HLA antibody screening and HLA typing. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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