Placental C4d deposition is a feature of defective placentation: Observations in cases of preeclampsia and miscarriage

Eun Na Kim, Bo Hyun Yoon, Joong Yeup Lee, Doyeong Hwang, Ki Chul Kim, Joon Ho Lee, Jae Yoon Shim, Chong Jai Kim

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18 Citations (Scopus)


Placental C4d deposition is frequent in preeclampsia, and shallow placentation is a characteristic of both preeclampsia and miscarriage. This study was conducted to determine the relationship among placental C4d, maternal human leukocyte antigen (HLA) antibodies, and placental pathology in preeclampsia and miscarriage cases. The patient population (N = 104) included those with (1) preterm preeclampsia with fetal growth restriction (PE-FGR; n = 21), (2) preterm preeclampsia (PE; n = 20), (3) spontaneous preterm delivery (sPTD; n = 39), and (4) miscarriage (n = 24). C4d immunohistochemistry was performed, and the presence of maternal plasma HLA antibodies was examined. C4d staining of the syncytiotrophoblast was more frequent in PE-FGR patients (76.2 %) than in PE (10.0 %; p < 0.001) and sPTD (2.6 %; p < 0.001) patients. Maternal HLA antibody-positive rate was not different among the study groups. There was a significant correlation between C4d immunoreactivity and placental pathology consistent with maternal vascular underperfusion (p < 0.001) but not with maternal HLA antibody status. In miscarriages, the positive rates of C4d, HLA class I, and HLA class II antibodies were 58.3, 25.0, and 12.5 %, respectively. There was no correlation between the presence of maternal HLA class I or II antibodies and placental C4d immunoreactivity. This study confirms frequent placental C4d deposition in preeclampsia with fetal growth restriction and miscarriage. The association between placental C4d deposition and pathological findings of maternal vascular underperfusion suggests that C4d staining of the syncytiotrophoblast is a consequence of defective placentation rather than of a specific maternal immune response against fetal HLA. The study also demonstrates the usefulness of C4d as a biomarker of placentas at risk.

Original languageEnglish
Pages (from-to)717-725
Number of pages9
JournalVirchows Archiv
Issue number6
Publication statusPublished - 2015 Jun 10

Bibliographical note

Funding Information:
This research was supported in part by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2012R1A2A2A01012368) and in part by a grant (14-521) from the Asan Institute for Life Sciences, Seoul, South Korea.

Publisher Copyright:
© Springer Science+Business Media Dordrecht 2015.

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology


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