Natural occurrence of human tumor-associated anti-fetal antibodies during normal pregnancy

Abstract

Human antibodies to human or mouse fetal liver cell antigens have been demonstrated in the sera of patients harboring carcinoma of the breast, lung colon and malignant melanoma. In order to define further the clinical significance of these tumor-associated anti-fetal antibodies, the same indirect radioimmunoassay detection technique has been used to examine sera obtained during normal pregnancy. In addition, studies have been directed at the immunochemical specificity of the underlying reaction. During pregnancy a specific pattern of reactivity related to parturition occurs as reflected by the absorption ratio (AR) in the isotopic antiglobulin test (IAT). Compared with a control group of ten nonpregnant females (AR 1.20 ± 0.17) there was significant reactivity among 11/11 pregnant patients at full term (AR 2.36 ± 0.31) and 10/10 patients one month postpartum (AR 3.03 ± 0.33). In contrast, 9/9 patients at 5–9 days postpartum demonstrated essentially the same reactivity (AR 1.29 ± 0.21) as the control group. A similar pattern of murine antifetal liver cell reactivity during the peripartum period was found in normal mice. The specificity of antibody binding in this system has been further investigated. Cross-adsorption experiments have demonstrated that whereas significant reduction of serum reactivity can be obtained through adsorption with fetal liver cells, no such adsorption could be obtained with adult human or mature mouse liver homogenates and spleen cells. Further, the absence of immunoglobulins of Fc receptor activity on unreacted fetal liver cells suggests that a specific antigen-antibody reaction is involved. Preliminary immunochemical characterization strongly supports the specificity of antibody binding activity.