title: The pathogenesis of villitis of unknown etiology: analysis with a new conjoint immunohistochemistry-in situ hybridization procedure to identify specific maternal and fetal cells.
abstract: The conjoint immunohistochemistry-in situ hybridization (IHC-ISH) procedure permits, under routine light microscopic conditions, simultaneous documentation of either a male or female karyotype plus the immunological phenotype of individual cells within paraffin-embedded tissues. We have used this technique to characterize the inflammatory response in placental villitis of unknown etiology (VUE). A male placenta with severe VUE and appropriate control placentas were analyzed. In situ hybridization probes concurrently label both the X and Y chromosomes. On the same tissue section, individual cells were characterized with antibodies to CD3, CD68, or CD20. The amnion and syncytiotrophoblast were delineated by cytokeratin antibody (AE1/AE3). A complete karyotyping was performed on amnion cells to validate the procedure. Amnion cell karyotyping confirmed the accuracy of the procedure. The VUE case revealed that 88.8% of intravillous CD3+ lymphocytes were female (maternal), while 11.2% were male (fetal). Intervillous CD3+ lymphocytes and CD68+ macrophages were universally female. Intravillous CD68+ cells were only 10.5% female. Perivillous CD68+ cells were 94.6% female. Remarkably, multinucleated giant cells were exclusively maternal. This study confirms that lymphocytes in VUE are predominately but not exclusively maternal T cells. Our findings indicate that invasion of fetal villi by maternal T cells is associated with focal destruction of the syncytiotrophoblast, clarifying how placental immuno-defensive mechanisms may be contravened.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
authors.forename: David
authors.initials: D
authors.lastname: Myerson
authors.forename: Rachael K
authors.initials: RK
authors.lastname: Parkin
authors.forename: Kurt
authors.initials: K
authors.lastname: Benirschke
authors.forename: Clifford N
authors.initials: CN
authors.lastname: Tschetter
authors.forename: Scott R
authors.initials: SR
authors.lastname: Hyde
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002824:Chorionic Villi / Q000378:metabolism / Q000473:pathology*; D041321:Chromosomes, Human, X; D041322:Chromosomes, Human, Y; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017403:In Situ Hybridization / Q000379:methods*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008431:Maternal-Fetal Exchange / Q000235:genetics / Q000276:immunology; D010922:Placenta Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
chemical_list: D015703:Antigens, CD; D015415:Biomarkers