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Published on: March 24, 2015
Patterns of Interferon γ Expression and C4d Deposition in Chronic Intervillositis of Unknown Etiology
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.
Abstract:
The pathogenesis of chronic intervillositis of unknown etiology (CIUE) may involve IFNγ overexpression. This study assesses the extent of IFNγ expression in CIUE by immunohistochemistry and compares it to spontaneous pregnancy losses. C4d deposition is also assessed to see whether IFNγ and C4d might represent separate diagnostic categories. Placenta from first to early second trimester with high grade CIUE (CHG; 17 cases) and low grade CIUE (CLG; 12 cases) is compared to euploid (SPLN; 18 cases), aneuploid spontaneous pregnancy losses (SPLA, 17 cases), normal placenta (NP, 13 cases). Protein level expression of IFNγ and C4d is assessed on whole tissue sections by immunohistochemistry. 35% of CHG and 42% of CLG show some level of IFNγ expression localized to the luminal surface of syncytiotrophoblast. 12% of SPLA and no SPLN or NP cases are IFNγ positive. C4d deposition is seen in 100% of CIUE, 88% of SPLA, 83% of SPLN, and 46% of NP samples. IFNγ overexpression occurs in approximately 40% of CIUE-related pregnancy losses. IFNγ expression restricted to a subgroup of CIUE implies that IFNγ may define a distinct disease process. The non-discriminatory pattern of C4d deposition suggests it is a non-specific phenomenon possibly related to placental damage.
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