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

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

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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
Volume466
Issue number6
DOIs
StatePublished - 10 Jun 2015

Fingerprint

Placentation
Spontaneous Abortion
HLA Antigens
Pre-Eclampsia
Mothers
Antibodies
Trophoblasts
Fetal Development
Blood Vessels
Pathology
Staining and Labeling
Histocompatibility Antigens Class I
Placenta
Biomarkers
Immunohistochemistry

Keywords

  • Complement C4d
  • HLA antigen
  • Placenta
  • Preeclampsia
  • Spontaneous abortion

Cite this

Kim, Eun Na ; Yoon, Bohyun ; Lee, Joong Yeup ; Hwang, Doyeong ; Kim, Ki Chul ; Lee, Joon Ho ; Shim, Jae Yoon ; Kim, Chong Jai. / Placental C4d deposition is a feature of defective placentation : Observations in cases of preeclampsia and miscarriage. In: Virchows Archiv. 2015 ; Vol. 466, No. 6. pp. 717-725.
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abstract = "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.",
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Placental C4d deposition is a feature of defective placentation : Observations in cases of preeclampsia and miscarriage. / Kim, Eun Na; Yoon, Bohyun; Lee, Joong Yeup; Hwang, Doyeong; Kim, Ki Chul; Lee, Joon Ho; Shim, Jae Yoon; Kim, Chong Jai.

In: Virchows Archiv, Vol. 466, No. 6, 10.06.2015, p. 717-725.

Research output: Contribution to journalArticle

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T1 - Placental C4d deposition is a feature of defective placentation

T2 - Observations in cases of preeclampsia and miscarriage

AU - Kim, Eun Na

AU - Yoon, Bohyun

AU - Lee, Joong Yeup

AU - Hwang, Doyeong

AU - Kim, Ki Chul

AU - Lee, Joon Ho

AU - Shim, Jae Yoon

AU - Kim, Chong Jai

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AB - 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.

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KW - HLA antigen

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