Antigens of human trophoblasts: A working hypothesis for their role in normal and abnormal pregnancies

Abstract

The preparation and characterization of antisera to human trophoblast membranes was described. Rabbit antisera were raised to trophoblast microvilli prepared by differential ultracentrifugation. Antibodies to serum proteins were removed by solid-phase immunoabsorption with normal human serum and indirect immunofluorescence experiments with cryostat sections of human placentas showed that the absorbed anti-trophoblast sera reacted with trophoblasts as well as with stromal cells and endothelium of chorionic villi. The antisera also produced membrane fluorescence when studied on viable lymphocytes and certain human cell lines. These anti-trophoblast sera were also lymphocytotoxic. This reaction was abolished by prior absorption of the antisera with leukocytes. The leukocyte-absorbed anti-trophoblast sera retained their ability to react with trophoblasts and certain human cell lines, but no longer reacted with lymphocytes or placental stromal cells and endothelium. Two categories of trophoblast membrane antigens are thus defined: 1 present on trophoblasts and certain human cell lines (tentatively designated TA1), and the other on trophoblasts and lymphocytes, villous fibroblasts, and endothelium (tentatively designated TA2). A working hypothesis was proposed stating that normal pregnancy involves the generation of anti-TA2 subsequent to blastocyst implantation and entrance of trophoblasts into the maternal circulation. This involves a mechanism similar to allogeneic cell stimulation and results in antibodies that block the recognition or cytotoxicity of TA1. Failure to mount this response allows TA1 recognition and trophoblast immunopathology.