Abstract
Antibody‐dependent cellular cytotoxicity (ADCC) was employed to detect and characterize an unusually high‐titered antibody to a paternal HLA antigen in a patient with gestational choriocarcinoma. Choriocarcinoma is a trophoblastic neoplasm of embryonic origin, and therefore genetically competent to express paternal histocompatibility antigens. However, normal human trophoblast is reported to lack HLA antigens. The demonstration of a high‐titre antibody to a paternal antigen is of interest for two reasons: it suggests that HLA antigens develop in trophoblast as a consequence of malignancy, and might therefore constitute a marker for neoplasia. Secondly, it indicates that a highly immunogenic antigen of tumor origin is provoking a humoral response, but that the disease is progressing in the face of such immunity. The antibody is distinguishable from that provoked by normal pregnancy in three ways. It is of exceedingly high titre (> 1:32,000 against paternal lymphoblast targets); it is monospecific for the paternal HLA B locus antigen 12; and it demonstrates a pronounced prozone indicative of the presence of immune complexes (ICs). Post‐partum sera from multiparous women frequently contain HLA antibodies demonstrable in ADCC. However, titres are comparatively low, the antibodies are not monospecific, but recognize HLA and other (Ia) antigens, and they do not show a marked prozone, or the presence of immune complexes. ICs were indeed demonstrable at a concentration of >25 μg/ml (aggregated human gamma globulin equivalents) by a modified Raji cell technique. Histological examination of the uterine tumor following hysterectomy revealed a high degree of mononuclear cell infiltration, suggestive of cell‐mediated immunity. The patient was quite capable of generating cytotoxic T‐cells to paternal lymphocytes on challenge in mixed lymphocyte culture, indicating that no general anergy or suppressor function was present. The possibility that suppression might be limited to the single B locus specificity sensitizing the patient's humoral response was not investigated. Since immune complexes interfere with both ADCC cytotoxicity and T‐cell cytotoxicity it is suggested that they might contribute to the lack of resistance to a demonstrably immunogenic allograft.