Expression Of Fetal Antigens Research Articles

Do monocyte ADCC assays accurately predict the severity of hemolytic disease of the newborn caused by antibodies to high-frequency antigens?

Abstract Monocyte ADCC assays are helpful indicators of the severity of hemolytic disease of the newborn (HDN) due to anti-D. It would be particularly useful if the assays also accurately predicted the ability of antibodies to high-frequency antigens (UFA) to cause HDN. To investigate this possibility, 14 antenatal sera containing antibodies to HFA were tested and the results correlated with the severity of HDN. Antibody titers were determined using an indirect antiglobulin test (IAT). Eight sera (anti-Hy, -Dib, -Jra -ScI, -Inb, -Wrb, and-U [n =2]) had low ADCC activity (< 28%) and did not cause HDN. The IAT titers ranged from 4 to 128. Two antibodies (anti-Ena and anti-Rh29) had high ADCC activity (≥ 72%) and high IAT titers (≥ 1,024), and both caused severe HDN. The remaining four antibodies (anti-Cra, -Inb, and -U [n = 2]) had ADCC activity ≥ 40 percent and titers ≥ 128, but they did not cause HDN. The inability of anti-Cra and anti-Inb to cause HDN is presumed to be related to fetal antigen expression and tissue distribution. The anti-Inb was further investigated using monocyte binding and inhibition studies. The absence of HDN in the presence of potent anti-U remains unexplained. In general, antibodies with low ADCC activity do not cause HDN, but high ADCC activity does not always indicate severe HDN. Immunohematology 1996;12:20-26.

Glomerular Lesions in Lymphomas and Leukemias

Renal lesions in lymphoid malignancies are rare, with most lesions observed in association with Hodgkin's disease. In two large series of patients with Hodgkin's disease, only 0.4 percent had minimal-change lesion whereas 0.1 percent had amyloidosis. The non-Hodgkin's lymphomas and leukemias comprise large and heterogeneous groups with equally diverse renal lesions. As in Hodgkin's disease, the most frequent lesion is minimal-change nephrotic syndrome. Also recognized are rare reports of renal disease associated with the atypical lymphoid proliferations of angioimmunoblastic lymphadenopathy, giant lymph node hyperplasia syndrome, and acquired immune deficiency syndrome. Broad generalizations regarding the pathogenesis of renal disease in these syndromes are difficult, partly due to the paucity and sporadic reporting of such cases. Mechanisms proposed to explain the renal pathologic findings include autologous nontumor antigens, tumor antigens, fetal antigen expression, immune complex deposition, viral antigens, and disordered T cell function.

Chicken fetal antigen expression on the definitive erythroid maturation series in the bone marrow of the adult chicken.

Chicken fetal antigen (CFA) describes a membrane developmental antigen system present on embryonic and fetal erythroid cells that is present during development, but is absent on erythrocytes of mature chickens. In this study, CFA was detected by indirect immunofluorescence and correlated with six stages of morphological maturation of erythroid cells. All cells in the erythroid series through the late polychromatic erythrocyte (reticulocyte) stage were found to possess CFA. Fluorescent intensity and staining patterns of the definitive erythroid series demonstrated CFA concentration increase and distribution pattern change throughout erythroid maturation.

Expression of fetal antigens in fetal and adult cells during long-term culture.

Expression of fetal antigens in early and late passages of tissue culture cells derived from C3H/HeN and C57BL/KaLw mouse fetal cells and from lung tissue of young C57BL/6N mice was investigated by the isotopic antiglobulin technique. The late passage lines of fetal cells had undergone "spontaneous" neoplastic transformation in culture. The antisera were produced by syngeneic immunization with 5000 R x-irradiated tissues from C3H/HeN and C57BL/6N fetuses of 1 to 2 weeks gestation. Fetal antigens were found to be retained even after 5 years in cell lines derived from fetal tissues. In these lines no consistent change in fetal antigen expression could be correlated with neoplastic transformation. In contrast, the early passages of adult cells did not have detectable amounts of fetal antigens. However, fetal antigen(s) was demonstrated in cells of the late passages, and cells of both lines grew as sarcomas when next assayed 55 days later. In addition, fetal antigens were also present in established tumor lines in culture.

Expression of Fetal Antigens by Normal Human Skin Cells Grown in Tissue Culture

Normal human sera are capable of causing complement-mediated lysis of normal human skin cells grown in tissue culture. This lytic reactivity can be completely removed by absorption with first trimester fetal tissue. Absorption with a variety of normal adult human tissues including lymphocytes, decidua, skin, and muscle are incapable of absorbing reactivity. Absorption of reactivity by fetal tissue is specific and not due to the introduction of anti-complementary or other nonspecific factors, as evidenced by the inability of simultaneous fetal absorption to remove reactivity from antisera with specificity for HLA antigens. Similarly, absorption of lytic sera with fetal calf serum proteins was incapable of removing reactivity against normal cells in tissue culture. It thus appears that normal human cells in tissue culture express antigens shared by the first trimester human fetus, but not present on a variety of adult human tissues. This "neoantigen" present on normal human cells when grown in tissue culture is a potential source of confusion and must be accounted for in searching for human tumor-specific antigens utilizing tissue culture cells.

Humoral antibody response and tumor transplantation resistance elicited by fetal tissues in mice.

Immune responses to fetal antigen immunization were studied in C57BL/6 (B6), C3H/HeN (C3H), and BALB/c (BALB) mice. In tests by the isotopic antiglobulin technique, the mice could be grouped in three classes according to their antibody responses: good responders (B6), poor responders (C3H), and nonresponders (BALB). In tumor transplantation experiments, protection against syngeneic tumor-cell challenge, after fetal tissue immunization, was observed only with B6 mice. In addition, experiments on B6 mice showed that resistance to tumor challenge after fetal tissue immunization depended on the quantitative expression of fetal antigens by the tumor cells. Our results indicated that, in addition to other well-known factors, the effectiveness of fetal tissue immunization in tumor-challenge resistance depended on both host responsiveness and the amount of fetal antigen expressed by the tumor cells.

Information Transfer and Sperm Uptake by Mammalian Somatic Cells

This chapter describes that sperm are endowed by their specific differentiation to interact with and to deliver their genetic components into ova for subsequent activation and function. Whether analogous genetic information can be transferred by sperm to mammalian somatic cells is unknown. The chapter describes that mammalian sperm interact with mammalian somatic cells as evidenced by actual penetration, the appearance of changes in morphology and growth characteristics, and the production of new gene products. These changes may be consequences of the direct acquisition and genetic expression of either the sperm chromatin itself or the reverse transcriptase containing complex within the sperm heads. The interaction of sperm with somatic cells that leads to fetal antigen expression and to changes resembling oncogenic transformation may involve a recapitulation, at least in part, of the program of postfertilization gene expression. The normal function of sperm is fertilization; the presence of its various components in somatic cells might very well induce changes analogous to those that occur in embryological and fetal development. It has been estimated that the amount of unique-sequence DNA that is transcribed in the rabbit blastocyst but no longer in the midgestation embryo is enough to specify some 23,000 different proteins; the corresponding difference between normal and virus-transformed mouse cells is regarded as sufficient to specify some 200,000 different proteins. To sort out the many steps involved in embryogenesis, fetal development, and oncogenesis in the face of such complexity is indeed a prodigious task.

Biochemical properties and replication of murine intracisternal A particles during early embryogenesis

Intracisternal A particles exhibit features which are characteristic of oncogenic RNA viruses and features which are reminiscent of fetal antigen expression. Evidence has been developed by ultrastructural study which points toward a vertical transmission of these particles, a situation analogous to known RNA tumor viruses. Intracisternal A particles are readily found in certain preimplantation mouse embryos; they are found occasionally in a variety of neoplasms. Biochemical properties of highly purified intracisternal A particles isolated from murine neuroblastoma cells or plasma cell tumor include high molecular weight 60–70S RNA and an RNA-dependent DNA polymerase. The enzymatic characterization of the A particle DNA polymerase is reported. The enzyme is found analogous to other C-type viral reverse transcriptase by virtue of its preference for Mn 2+ activation and certain DNA-RNA hybrid templates, oligo dT 12 ·poly rA (dT 12 ·rA n) and oligo dG 12 ·poly rC (dG 12 ·rC n), for the stimulation of its activity. The endogenous reaction of the A particle RNA-dependent DNA polymerase produces a DNA transcript of its intrinsic RNA with base complementarity as demonstrated by the results of hybridization studies. The control of the expression of this gene entity and its relevance to malignant transformation constitute a problem worthy of further investigation.

Expression of fetal antigens and tumor-specific antigens in SV40-transformed cells. I. Serological analysis of the antigenic specificities.

AbstractThe fetal antigens expressed in a variety of tumors have previously been shown to be different from tumor‐specific antigens. The present study on the expression of fetal antigens in various SV40‐transformed cells showed that more than one fetal antigen may be found in these cell lines, and that the expression of fetal antigens was not directly related to the function of the SV40 genome. These fetal antigens were not found in syngeneic spleen cells but were found in the normal spleens of some other strains of mice.

Expression of fetal antigens and tumor-specific antigens in SV40-transformed cells. II. Tumor transplantation studies.

AbstractThe effect of immunization with fetal antigens and tumor‐specific antigens on the transplantation of SVT2, a BALB/c mouse tumor induced by Simian virus 40 (SV40), has been studied. Hyperimmunization with 5,000 R X‐irradiated, syngeneic fetuses of 1–2 weeks' gestation or syngeneic spleen cells gave no protection to SVT2 cell challenge. In contrast, immunization with SV40 or SV40‐transformed cells gave a 100‐ to 1,000‐fold protection. These results gave additional evidence that fetal antigens are different from tumor‐specific transplantation antigen (TSTA).

Expression of fetal antigens in tumor cells

Expression of fetal antigens in tumor cells

Expression of fetal antigens in tumor cells.

The activities of sera that reacted specifically with the specific cell-surface antigens of polyoma or simian virus 40 tumors could only be inhibited by absorption of the sera with tumor cells transformed by the specific virus, and could not be removed by the absorption with cells from various fetal tissues nor with cells from other tumors. In contrasts, the antisera produced in male C3H/HeN mice by inoculation of irradiated, syngeneic fetal tissue of 1- to 2-weeks gestation, reacted with various tumor cells. The activities of these sera, when tested against cells from tumors induced by polyoma virus or simian virus 40, could also be removed by absorption with cells from tumors induced by viruses other than polyoma or simian virus 40, including leukemia cells induced by Gross virus (C58NT)D, Rauscher virus (RBL-5), and by dimethylbenzanthrene (EL. 4), and cells from mammary tumors (MM102), plasma-cell tumors (MPC-113), and fetal tissues. These results indicated that fetal antigens may be expressed in tumor cells, but they are different from tumor-specific antigens that are specific for a particular tumor or for tumors induced by a particular virus.