Placental Complement Activation in Fetal and Neonatal Alloimmune Thrombocytopenia: An Observational Study

Thijs W de Vos, Dian Winkelhorst, Hans J Baelde, Kyra L Dijkstra, Rianne D M van Bergen, Lotte E van der Meeren, Peter G J Nikkels, Leendert Porcelijn, C Ellen van der Schoot, Gestur Vidarsson, Michael Eikmans, Rick Kapur, Carin van der Keur, Leendert A Trouw, Dick Oepkes, Enrico Lopriore, Marie-Louise P van der Hoorn, Manon Bos, Masja de Haas

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Abstract

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that causes thrombocytopenia 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.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume22
Issue number13
DOIs
Publication statusPublished - 23 Jun 2021
Externally publishedYes

Bibliographical note

Funding:
Funded by Fonds Gezond Geboren (E50-03-LUMC) and Process and Product Development
Diagnostic Services, Sanquin (SQI/00034).

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