The immunological basis of villitis of unknown etiology - review

Placenta. 2013 Oct;34(10):846-55. doi: 10.1016/j.placenta.2013.07.002. Epub 2013 Jul 26.


Villitis of unknown etiology (VUE) represents a common placental inflammatory lesion, primarily, but not exclusively, identifiable T lymphocytes at term. Despite considerable evidence to contest that this simply represents a benign pathological finding, VUE remains a significantly undervalued diagnosis. Given its association with adverse pregnancy outcomes; including fetal growth restriction, preterm birth, and recurrent pregnancy loss, an increased awareness amongst clinician obstetricians is certainly warranted. The underlying immunopathogenesis of VUE remains uncertain. Despite initial theories that this represents an infectious placental lesion of undiagnosed pathogenic source, a more complex sequence of events involving the "breakdown" of maternal-fetal tolerance is emerging. Characterization of a unique inflammatory phenomenon in which both maternal and fetal T lymphocytes and Höfbauer cells interact has captivated particular research interest and has generated analogies to both the problems of allograft rejection and graft-versus-host disease (GvHD). Within the context of VUE, this review evaluates how disruption of the multidimensional immunological mechanisms underlying feto-maternal tolerance may permit abnormal lymphocyte infiltration into placental villi. We shall review the existing evidence for these events in VUE and outline areas of certain future interest.

Keywords: APCs; Ab; Adverse fetal outcome; BMI; CP; GM-CSF; GvHD; Höfbauer cells; ICAM-1; IDO; IFNγ; IUGR; IVF; MHC; Maternale–fetal tolerance; NI; NK; PTL; Placental inflammation; Placental villi; SGA; SLE; T regulatory cells; T ymphocytes; T-helper; TNFα; TReg cells; Th; VUE; Villitis of unknown etiology; antibody; antigen presenting cells; body mass index; cerebral palsy; graft-versus-host disease; granulocyte-macrophage colony-stimulating factor; indoleamine 2,3-dioxygenase; intercellular adhesion molecule 1; interferon-γ; intra-uterine growth restriction; in vitro fertilization; major histocompatibility complex; natural killer; neurological impairment; pre-term labor; small for gestational age; systemic lupus erythematosis; tumor necrosis factor α.

Publication types

  • Review

MeSH terms

  • Abortion, Habitual / immunology
  • Chorionic Villi / immunology*
  • Chorionic Villi / pathology
  • Female
  • Fetal Growth Retardation / pathology
  • Fetus / immunology
  • Humans
  • Immune Tolerance / immunology
  • Maternal-Fetal Exchange / immunology
  • Placenta Diseases / immunology*
  • Placenta Diseases / pathology
  • Pregnancy / immunology*
  • Pregnancy Outcome
  • Premature Birth / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology