The Pathogenesis of Villitis of Unknown Etiology: Analysis with a New Conjoint Immunohistochemistry-in Situ Hybridization Procedure to Identify Specific Maternal and Fetal Cells

Author:

Myerson David12,Parkin Rachael K.1,Benirschke Kurt3,Tschetter Clifford N.4,Hyde Scott R.5

Affiliation:

1. Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA

2. University of Washington, Seattle, WA 98195, USA

3. University California San Diego Medical Center, San Diego, CA 92103, USA

4. St. Rose Hospital, Hayward, CA 94545, USA

5. Saint Francis Hospital, Tulsa, OK 74136, USA

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 immunodefensive mechanisms may be contravened.

Publisher

SAGE Publications

Subject

General Medicine,Pathology and Forensic Medicine,Pediatrics, Perinatology and Child Health

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