Patterns of Interferon γ Expression and C4d Deposition in Chronic Intervillositis of Unknown Etiology

Jefferson Terry1

  • 1Department of Pathology, British Columbia Children's and Women's Hospitals, Vancouver, BC, Canada.

Insights

Interferon-gamma (IFNγ) overexpression is observed in about 40% of chronic intervillositis of unknown etiology (CIUE) pregnancy losses. This suggests IFNγ may define a distinct CIUE disease process, separate from non-specific C4d deposition.

Area of Science:

  • Reproductive immunology
  • Pathology
  • Immunohistochemistry

Background:

  • Chronic intervillositis of unknown etiology (CIUE) is a pregnancy complication potentially linked to interferon-gamma (IFNγ) overexpression.
  • Assessing IFNγ and C4d deposition in placental tissues can help elucidate CIUE pathogenesis and diagnostic markers.

Purpose of the Study:

  • To quantify IFNγ expression in high-grade (CHG) and low-grade (CLG) CIUE placentas.
  • To compare IFNγ and C4d deposition in CIUE with spontaneous pregnancy losses (euploid and aneuploid) and normal placentas.
  • To investigate if IFNγ and C4d represent distinct diagnostic categories in pregnancy loss.

Main Methods:

  • Immunohistochemistry was used to assess protein-level expression of IFNγ and C4d in placental tissues.
  • Placental samples included CHG (n=17), CLG (n=12), spontaneous euploid pregnancy loss (SPLN, n=18), spontaneous aneuploid pregnancy loss (SPLA, n=17), and normal placenta (NP, n=13).

Main Results:

  • IFNγ expression was detected in 35% of CHG and 42% of CLG cases, localized to the syncytiotrophoblast.
  • IFNγ was positive in 12% of SPLA cases, but not in SPLN or NP cases.
  • C4d deposition was prevalent across all groups: 100% in CIUE, 88% in SPLA, 83% in SPLN, and 46% in NP.

Conclusions:

  • Approximately 40% of CIUE-related pregnancy losses exhibit IFNγ overexpression.
  • IFNγ expression appears restricted to a subgroup of CIUE, suggesting it may define a specific disease process.
  • C4d deposition shows a non-specific pattern, likely indicating placental damage rather than a distinct etiology.