Expression of retrovirus-related antigen in pregnancy. I. Antigens cross-reacting with simian retroviruses in human foetal tissues and cord blood lymphocytes.

Antisera to Mason-Pfizer or Baboon Endogenous Virus possessed complement-dependent cytotoxicity for cell lines chronically infected with these viruses, with some degree of cross-reaction. When appropriately absorbed with virus-free cells, the antisera were not cytotoxic for lymphocytes of adult males but lysed lymphocytes of neonates in about half of the 30 cord blood samples tested and were also cytotoxic for one third of 26 trophoblast suspensions prepared from healthy placentae. Detection of retrovirus-related antigens was no more frequent in trophoblast from 9 pre-eclamptic placentae. These viral antigens were also demonstrated in cultures of foetal tissues, but only after a period of culture and only when the cells were treated with 5-iododeoxyuridine. The results demonstrate that retroviruses are not only expressed in vivo in the placenta but can also be induced in cultures of foetal cells. Retrovirus-related antigens also seem to be present on foetal lymphocytes.

Expression of retrovirus-related antigen in pregnancy. II. Cytotoxic and blocking specificities of immunoglobulins eluted from the placenta.

Immunoglobulins, mostly of the IgG class, were detected in eluates of the placenta of 75% of 50 healthy women in their first or second pregnancy, 92% of 30 women with more than two pregnancies, and 87% of 23 pre-eclamptic patients. The immunoglobulins were assayed for complement-dependent cytotoxicity on human and monkey cell-lines, as well as on the same cells chronically infected with either Mason-Pfizer Virus (M-P V) or Baboon Endogenous Virus (BeV). The frequency of cytotoxic reactions was very low, except with immunoglobulins from the pre-eclamptic placentae, where one third of the samples lysed virus-infected cells with occasional killing of virus-free cells. All placental immunoglobulins which were not cytotoxic were then assayed for blocking activity by testing whether they could compete with the action of anticellular sera of virus-free cells, or with the toxic effect of antiviral sera on virus producing cells. 64% of the immunoglobulins from normal placentae competed with antiviral antibodies while only 17% blocked the action of anticellular sera. The frequency of blocking immunoglobulins was no greater in eluates from pre-eclamptic placentae. The data indicate that the placenta possesses retrovirus antigen sites which bind blocking antibodies in normal pregnancy and complement-dependent cytotoxic antibodies in pre-eclampsia.

Enhancement of the amylase-creatinine clearance ratio in pregnancy.

The renal clearance of amylase, expressed as a proportion of simultaneous creatinine clearance (Cam/-Ccr), was determined in 131 women in various stages of pregnancy. No abnormal serum levels of amylase were found. A moderate but significant increase in Cam/Ccr occurred during the last 15 weeks of pregnancy. Possible causes for this change were investigated in smaller groups of subjects. No increase in rapidly cleared isoamylase could be detected. No modification in renal tubular handling of protein could be evidenced, as assessed by measurements of the renal clearance of beta 2 microglobulin, expressed as a proportion of simultaneous creatinine clearance. An incrased glomerular permeability to amylase probably accounts for elevated Cam/Ccr in pregnancy.

Cell-mediated immune response to simian oncornavirus antigens in pregnant women.

Tritiated thymidine incorporation into lymphocytes of 118 adult women was studied in the presence of mitomycin C-treated cells prepared from cell lines continuously producing Mason-Pfizer monkey virus (MPMV), baboon C-particle virus, or simian sarcoma virus (SSV) and in the presence of control cell lines documented for the absence of oncornaviruses. At the end of pregnancy, women who had 5-9 pregnancies showed a high frequency (53%) of specific positive responses to cells with MPMV antigens. The frequencies were 15% for pregnant women with smaller numbers of pregnancies and 3% for nonpregnant women with similar numbers of previous pregnancies as in the pregnancy group. None of these nonpregnant women had lymphocytes responding to stimulation by baboon C-virus antigens, but positive responses were obtained in 20 and 16% of the pregnant groups, respectively. No correlation was found between responses to MPMV or baboon C-virus antigens. Of 48 women (35 pregnant, 13 nonpregnant) who were tested for lymphocyte responses to SSV antigens, only 2 showed a positive response. The results indicated that two distinct antigens, related to MPMV and to baboon C-virus, may be expressed during pregnancy and may then induce a transient cell-mediated response.