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

The pathogenesis of chronic intervillositis of unknown etiology (CIUE) may involve IFN gamma overexpression. This study assesses the extent of IFN gamma expression in CIUE by immunohistochemistry and compares it to spontaneous pregnancy losses. C4d deposition is also assessed to see whether IFN gamma 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 IFN gamma and C4d is assessed on whole tissue sections by immunohistochemistry. 35% of CHG and 42% of CLG show some level of IFN gamma expression localized to the luminal surface of syncytiotrophoblast. 12% of SPLA and no SPLN or NP cases are IFN gamma positive. C4d deposition is seen in 100% of CIUE, 88% of SPLA, 83% of SPLN, and 46% of NP samples. IFN gamma overexpression occurs in approximately 40% of CIUE-related pregnancy losses. IFN gamma expression restricted to a subgroup of CIUE implies that IFN gamma 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.