Positive C4d immunostaining of placental villous syncytiotrophoblasts supports host-versus-graft rejection in villitis of unknown etiology

Erin Rudzinski, Meghan Gilroy, Colin Newbill, Terry Morgan

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Chronic villitis of unknown etiology (VUE) occurs in 5% of placentas submitted to pathology and is characterized by lymphohistiocytic infiltration of chorionic villi. VUE is associated with fetal growth restriction, preterm birth, and recurrent pregnancy loss. Accumulating evidence indicates that VUE may represent a host-versus-graft reaction analogous to transplant rejection. Pathologists routinely screen for antibody-mediated rejection in transplant biopsies by immunostaining for C4d, which highlights the recognition of donor cells by the host immune system. Since the hemochorial placenta is bathed in maternal blood, we hypothesized that cases of VUE may show C4d deposition onto villous syncytiotrophoblasts (STB). Chronic villitis was diagnosed in 82 of 1986 (4%) singleton placentas submitted to our department from 2007 through 2011. Forty randomly selected cases were gestational age-matched with 40 negative controls. Patient charts were reviewed and representative placental sections were immunostained for C4d. A positive C4d result was defined as circumferential immunostaining of the STB around at least one villous, or strong staining of fetal endothelial cells in the chorionic plate or stem villi. Our data indicate that VUE usually occurs in the 3rd trimester (37 ± 0.5 weeks) and is associated with significantly reduced placental weight (P = 0.006). Positive C4d staining of STB was more common in VUE (35/40, 88%) compared with negative controls (2/40, 5%) (P <0.0001). It was also more common in multiparous (35/66, 53%) than primiparous (2/14, 14%) women (P <0.01). Although the precise mechanism remains to be determined, our data support the hypothesis that VUE may represent host-versus-graft rejection by the mother.

Original languageEnglish (US)
Pages (from-to)7-13
Number of pages7
JournalPediatric and Developmental Pathology
Volume16
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Trophoblasts
Graft Rejection
Placenta
Mothers
Staining and Labeling
Chorionic Villi
Premature Birth
Fetal Development
Gestational Age
Immune System
Endothelial Cells
Tissue Donors
Pathology
Transplants
Biopsy
Weights and Measures
Pregnancy
Antibodies

Keywords

  • C4d
  • Host-versus-graft rejection
  • Placenta
  • Villitis of unknown etiology

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine

Cite this

Positive C4d immunostaining of placental villous syncytiotrophoblasts supports host-versus-graft rejection in villitis of unknown etiology. / Rudzinski, Erin; Gilroy, Meghan; Newbill, Colin; Morgan, Terry.

In: Pediatric and Developmental Pathology, Vol. 16, No. 1, 01.2013, p. 7-13.

Research output: Contribution to journalArticle

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abstract = "Chronic villitis of unknown etiology (VUE) occurs in 5{\%} of placentas submitted to pathology and is characterized by lymphohistiocytic infiltration of chorionic villi. VUE is associated with fetal growth restriction, preterm birth, and recurrent pregnancy loss. Accumulating evidence indicates that VUE may represent a host-versus-graft reaction analogous to transplant rejection. Pathologists routinely screen for antibody-mediated rejection in transplant biopsies by immunostaining for C4d, which highlights the recognition of donor cells by the host immune system. Since the hemochorial placenta is bathed in maternal blood, we hypothesized that cases of VUE may show C4d deposition onto villous syncytiotrophoblasts (STB). Chronic villitis was diagnosed in 82 of 1986 (4{\%}) singleton placentas submitted to our department from 2007 through 2011. Forty randomly selected cases were gestational age-matched with 40 negative controls. Patient charts were reviewed and representative placental sections were immunostained for C4d. A positive C4d result was defined as circumferential immunostaining of the STB around at least one villous, or strong staining of fetal endothelial cells in the chorionic plate or stem villi. Our data indicate that VUE usually occurs in the 3rd trimester (37 ± 0.5 weeks) and is associated with significantly reduced placental weight (P = 0.006). Positive C4d staining of STB was more common in VUE (35/40, 88{\%}) compared with negative controls (2/40, 5{\%}) (P <0.0001). It was also more common in multiparous (35/66, 53{\%}) than primiparous (2/14, 14{\%}) women (P <0.01). Although the precise mechanism remains to be determined, our data support the hypothesis that VUE may represent host-versus-graft rejection by the mother.",
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