Chronic histiocytic intervillositis: A breakdown in immune tolerance comparable to allograft rejection?

Am J Reprod Immunol. 2021 Mar;85(3):e13373. doi: 10.1111/aji.13373. Epub 2020 Nov 24.

Abstract

Chronic histiocytic intervillositis (CHI) is a pregnancy disorder characterized by infiltration of maternal macrophages into the intervillous space of the human placenta, often with accompanying perivillous fibrin deposition. CHI is associated strongly with foetal growth restriction and increased risk of miscarriage and stillbirth. Although rare, affecting 6 in every 10 000 pregnancies beyond 12 weeks' gestation, the rate of recurrence is high at 25%-100%. To date, diagnosis of CHI can only be made post-delivery upon examination of the placenta due to a lack of diagnostic biomarkers, and criteria vary across publications. No treatment options have shown proven efficacy, and CHI remains a serious obstetric conundrum. Although its underlying aetiology is unclear, due to the presence of maternal macrophages and the reported increased incidence in women with autoimmune disease, CHI is hypothesized to be an inappropriate immune response to the semi-allogeneic foetus. Given this lack of understanding, treatment approaches remain experimental with limited rationale. However, there is recent evidence that immunosuppression and antithrombotic therapies may be effective in preventing recurrence of associated adverse pregnancy outcomes. With similarities noted between the pathological features of CHI and acute rejection of solid organ transplants, further investigation of this hypothesis may provide a basis for tackling CHI and other immune-related placental conditions. This review will explore parallels between CHI and allograft rejection and identify areas requiring further confirmation and exploitation of this comparison.

Keywords: HLA; graft rejection; macrophages; miscarriage; placenta; pregnancy; stillbirth.

Publication types

  • Review

MeSH terms

  • Allografts / immunology
  • Autoimmune Diseases / immunology*
  • Chorionic Villi / pathology*
  • Chronic Disease
  • Female
  • Graft Rejection / immunology*
  • Histiocytes / pathology*
  • Humans
  • Immune Tolerance
  • Maternal Exposure / adverse effects
  • Placenta Diseases / immunology*
  • Pregnancy / immunology*
  • Pregnancy Complications / immunology*