Virtual crossmatching reveals upregulation of placental HLA-Class II in chronic histiocytic intervillositis

Sci Rep. 2024 Aug 12;14(1):18714. doi: 10.1038/s41598-024-69315-5.

Abstract

Chronic histiocytic intervillositis (CHI) is a recurrent placental lesion where maternal macrophages infiltrate the intervillous space. Its cause is unknown, though due to similarities to rejected allografts one hypothesis is that CHI represents maternal-fetal rejection. Here, virtual crossmatching was applied to healthy pregnancies and those with a history of CHI. Anti-HLA antibodies, measured by Luminex, were present in slightly more controls than CHI (8/17 (47.1%) vs 5/14 (35.7%)), but there was no significant difference in levels of sensitisation or fetal specific antibodies. Quantification of immunohistochemical staining for HLA-Class II was increased in syncytiotrophoblast of placentas with CHI (Grade 0.44 [IQR 0.1-0.7]) compared to healthy controls (0.06 [IQR 0-0.2]) and subsequent pregnancies (0.13 [IQR 0-0.3]) (P = 0.0004). HLA-Class II expression was positively related both to the severity of CHI (r = 0.67) and C4d deposition (r = 0.48). There was no difference in overall C4d and HLA-Class I immunostaining. Though increased anti-HLA antibodies were not evident in CHI, increased expression of HLA-Class II at the maternal-fetal interface suggests that they may be relevant in its pathogenesis. Further investigation of antibodies immediately after diagnosis is warranted in a larger cohort of CHI cases to better understand the role of HLA in its pathophysiology.

MeSH terms

  • Adult
  • Chorionic Villi / immunology
  • Chorionic Villi / metabolism
  • Chorionic Villi / pathology
  • Chronic Disease
  • Female
  • Histocompatibility Antigens Class II* / metabolism
  • Humans
  • Placenta / immunology
  • Placenta / metabolism
  • Placenta / pathology
  • Placenta Diseases / immunology
  • Placenta Diseases / metabolism
  • Placenta Diseases / pathology
  • Pregnancy
  • Trophoblasts / immunology
  • Trophoblasts / metabolism
  • Trophoblasts / pathology
  • Up-Regulation

Substances

  • Histocompatibility Antigens Class II