TY - JOUR
T1 - Placental complement activation in fetal and neonatal alloimmune thrombocytopenia
T2 - An observational study
AU - de Vos, Thijs W.
AU - Winkelhorst, Dian
AU - Baelde, Hans J.
AU - Dijkstra, Kyra L.
AU - van Bergen, Rianne D.M.
AU - van der Meeren, Lotte E.
AU - Nikkels, Peter G.J.
AU - Porcelijn, Leendert
AU - van der Schoot, C. Ellen
AU - Vidarsson, Gestur
AU - Eikmans, Michael
AU - Kapur, Rick
AU - van der Keur, Carin
AU - Trouw, Leendert A.
AU - Oepkes, Dick
AU - Lopriore, Enrico
AU - van der Hoorn, Marie Louise P.
AU - Bos, Manon
AU - de Haas, Masja
N1 - 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.
PY - 2021/7/1
Y1 - 2021/7/1
N2 - 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. 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.
AB - 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. 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.
KW - Alloimmunization during pregnancy
KW - Classical pathway complement activation
KW - Fetal growth restriction
KW - Fetal neonatal alloimmune thrombocytopenia
KW - Histopathology placenta
KW - Placental dysfunction
KW - Fetus/immunology
KW - Placenta/immunology
KW - Humans
KW - Histocompatibility Antigens Class I/immunology
KW - Male
KW - Case-Control Studies
KW - Pregnancy
KW - Complement Activation/immunology
KW - Antibodies/immunology
KW - Thrombocytopenia, Neonatal Alloimmune/immunology
KW - Adult
KW - Female
KW - Immunoglobulins, Intravenous/immunology
KW - Retrospective Studies
KW - Infant, Newborn
KW - fetal neonatal alloimmune thrombocytopenia
KW - histopathology placenta
KW - placental dysfunction
KW - fetal growth restriction
KW - classical pathway complement activation
KW - alloimmunization during pregnancy
UR - http://www.scopus.com/inward/record.url?scp=85108270831&partnerID=8YFLogxK
U2 - 10.3390/ijms22136763
DO - 10.3390/ijms22136763
M3 - Article
C2 - 34201864
AN - SCOPUS:85108270831
SN - 1661-6596
VL - 22
SP - 1
EP - 11
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 13
M1 - 6763
ER -