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Biomedical subjects

M F Reznikoff-Etievant

Publications and source records attributed to M F Reznikoff-Etievant.

At least 19 recordsLinked to original sources

IFN-gamma induces apoptosis in mouse embryonic stem cells, a putative mechanism of its embryotoxicity.

It has been reported that interferon (IFN)-gamma should inhibit in vitro mouse embryo growth by direct cell toxicity. However, the mechanism involved has not been clearly established. In the present study, this question was addressed using the embryonic stem (ES) cell model. It was found that IFN-gamma, induces a dose-dependent apoptosis in ES cells, as assessed by trypan-blue staining, by Annexin-V labeling and DNA analysis, Moreover, IFN-gamma treatment cooperates with Fas-mediated apoptosis, a phenomenon that has been recently reported. As Bcl-2 oncoprotein functions as a death repressor molecule in an evolutionarily conserved cell death pathway, its expression was analyzed by flow cytometry. It was demonstrated that Bcl-2 is expressed in ES cells. When compared to untreated ES cells, IFN-gamma-treated, apoptotic cells expressed a lower Bcl-2 level and a normal level of Fas, whereas surviving cells expressed a normal level of Bcl-2 but a lower Fas expression. Altogether, these data suggest that IFN-gamma may influence early mouse embryo development by promoting apoptosis, which may constitute a novel mechanism of IFN-gamma embryotoxicity.

Animals↗

Habitual abortions in 678 healthy patients: investigation and prevention.

The objective of this study of patients with habitual abortion (HA), was to determine their autoimmune profile and to try to prevent new abortions using low-dose aspirin for 7 months with prednisone in the first trimester only, or with low-dose aspirin alone. A total of 678 healthy patients with three or more HA were investigated for antiphospholipid antibodies, antinuclear and antithyroid antibodies. Among these patients, 277 pregnant women were treated, 214 were given prednisone and aspirin (161 autoantibody-negative and 53 autoantibody-positive women), and 63 autoantibody-negative women received aspirin alone. Autoantibodies were present in 33.9% of the patients, in 82.6% of them anticardiolipin antibodies were found to be isolated or associated with antiprothrombin, antithyroid, circulating anticoagulant, antinuclear or anti-beta2 glycoprotein 1 antibodies. In autoantibody-negative pregnant women treated by prednisone and aspirin or aspirin alone, the success rate of live births was 90.7% (146 out of 161) and 74.6% (47 out of 63) respectively (P < 0.01). In autoantibody-positive patients treated with prednisone and aspirin the success rate was 84.9% (45 out of 53) (not significant). Prednisone and aspirin seemed to be as efficient in autoantibody-negative or positive women but better than aspirin alone in autoantibody-negative women. A double-blind trial is in progress to confirm these results.

Abortion, Habitual↗

[Embryotoxic factors and recurrent spontaneous abortions].

About 30% of recurrent spontaneous abortions remain unexplained by traditional or biological anomalies. The purpose of this work was to investigate embryotoxic factors produced by trophoblast stimulated lymphocytes from women with unexplained recurrent spontaneous abortion. The samples from 36 women with recurrent abortion before and during the next pregnancy and from 7 women with normal pregnancies and no history of spontaneous abortion have been tested. The lymphocytes were stimulated with trophoblastic extracts. The supernatants of the stimulated lymphocytes were tested in a 4-cell mouse embryo culture. The secretion of embryotoxic factor was determined if the number of life blastocysts was less than 50% of control values after 4 days. The lymphocytes from 59% women with 3 or more recurrent abortion produced the embryotoxic factor, this factor may be useful in predicting pregnancy outcome in women with a history of unexplained recurrent miscarriage. The embryotoxic factor might be a new cause of recurrent abortion and a predictive factor.

Abortion, Habitual↗

No evidence for the expression of the progesterone receptor on peripheral blood lymphocytes during pregnancy.

The expression of the progesterone receptor in human peripheral blood lymphocytes was analysed, using an enzyme linked immunosorbent assay (Abbott PgR-EIA monoclonal), in order to evaluate its prognostic character in the context of spontaneous abortion. Cytosols were prepared from lymphocytes of 24 healthy pregnant women (11 first, 10 second and three third trimester), seven healthy non-pregnant women, nine women with recurrent spontaneous abortion, and six healthy men. In addition, a human breast carcinoma cell line (ZR-75-1), which expresses the progesterone receptor, was analysed throughout. The ZR-75-1 cell line showed an expression of 642 fmol/mg whereas lymphocytes of pregnant women showed an expression < or = 4 fmol/mg. Lymphocytes of non-pregnant women, women with threatened pre-term delivery, and men showed equivalent levels: 3 +/- 1, 3 +/- 2 and 5 +/- 4 fmol/mg respectively. These results show that there is no evidence of specific expression of the progesterone receptor in pregnancy and exclude any prognostic character in spontaneous abortion. A role for the progesterone receptor in the mechanism of the known effect of progesterone on peripheral blood lymphocytes is also excluded.

Abortion, Habitual↗

HLA antigen-sharing in couples with repeated spontaneous abortions and the birthweight of babies in successful pregnancies.

Previously, several groups reported an increase in HLA antigen-sharing in couples suffering from unexplained repeated spontaneous abortions. It was felt necessary to find out if HLA sharing could have any effect on children born after a successful pregnancy. The birthweight figures of children of 76 couples with repeated spontaneous abortions were analyzed. The results show a significantly lower birthweight in babies born from those couples, presenting a high incidence of HLA antigen-sharing, particularly concerning class II antigens.

Abortion, Habitual↗

HLA-DRw52a is involved in alloimmunization against PL-A1 antigen.

The alloimmunization against the platelet PL-A1 antigen is strongly associated with a HLA class II structure in mothers of thrombocytopenic neonates. Most of the immunized women have first been shown to possess the DR3 specificity and subsequently the DRw52 allele. The 18 immunized mothers studied here by restriction fragment length polymorphism analysis had the DRw52a specificity at the DRB3 locus whatever their HLA-DRB1 gene product. This finding strongly suggests that the DRB3 chain is directly involved in the presentation of the PL-A1 antigen to the specific T cell. In addition, the similarities between DR3 and DRw52 structures due to a hypothetical gene conversion event should be considered in order to understand the high frequency of DR3 among the DRw52a-responding women. Alternatively, the high frequency of DR3 among the DRw52-responding mothers might be due to the high responder status associated with the former specificity.

Antigens, Human Platelet↗

Lymphocytic progesterone receptors in normal and pathological human pregnancy.

The progesterone receptor-specific monoclonal antibody (MoAb) mPRI was tested for its reactivity towards peripheral blood lymphocytes (PBL) of 49 healthy pregnant women, nine pregnant women with clinical symptoms of threatened preterm delivery, seven women with recurrent spontaneous abortion, ten women in labour and ten women with spontaneous abortion. Lymphocytes of 12 healthy age-matched non-pregnant volunteers were used as controls. Lymphocytes of nine healthy pregnant women at the 1st trimester of pregnancy and those of two non-pregnant donors were tested for the presence of estrogen and progesterone receptors by enzyme immunoassay. PBL of healthy pregnant women contained significantly more positive cells than those of non-pregnant controls. Furthermore, the number of receptor-containing cells increased in parallel with gestational age. In blood samples drawn during labour, as well as in those obtained from women with spontaneous abortion or clinical symptoms of threatened pre-term delivery, the percentage of positively stained lymphocytes was significantly lower than normal pregnancy values. This was also the case in peripheral blood of pregnant women with a history of recurrent spontaneous abortions.

Abortion, Habitual↗

Management of alloimmune neonatal and antenatal thrombocytopenia.

Neonatal and antenatal alloimmune thrombocytopenia is induced by maternal antibodies against platelet-specific fetal antigens. This disease is rare but potentially severe because of intracranial bleedings which may occur during pregnancy or around birth. In the last decade our knowledge of this disorder has markedly advanced. New techniques are used in platelet immunology. New platelet antigens involved in these perinatal thrombocytopenias have recently been discovered. A group of women likely to produce the responsible platelet antibodies has been genetically defined as regards the PLA1 antigen. The quality of the sonographies and the possibility of performing cord vein puncture in early pregnancy afford a new approach in the management of perinatal alloimmune thrombocytopenias. But more must be done to prevent the complications of this disease.

Blood Group Incompatibility↗

[Abortions of immunologic origin].

The immunology of pregnancy involves a series of systemic and above all local events, at the feto-maternal interface. These immunological events may explain the paradoxical non-rejection and development of the allogeneic conceptus within of the maternal body. The immunodeviation of the maternal immune system towards fetal tolerance may be altered or insufficient leading to true abortive diseases. The alteration of this tolerance may be the result of auto-immune abnormalities, particularly when autoantibodies are discovered in woman's serum. These antibodies are the antithromboplastin, antiphospholipid and antinuclear antibodies. They can be responsible for abortion even if the clinical symptoms of the lupus disease are absent. Abortive events occur at all stages of pregnancy. Table 1 shows that abortions with autoantibodies are more frequent when the accident occurs in the late stage of pregnancy. The therapy with corticoids and aspirin will be modulated in connection with the results. The second immune etiology is an insufficient production of immunological events usually involved in normal pregnancies. The current means available to detect this incompetency are imperfect because only systemic factors may be explored when local events are the most involved. We found a good correlation, in these women with recurrent early abortions of unknown etiology, between the production of anti-husband lymphocytes (AAP) and the success of a subsequent pregnancy. Women who suffer from recurrent spontaneous abortions of unknown etiology, without autoimmune abnormalities and without antipaternal antibodies (AAP), may profit from a therapy using the husband's leucocyte injections, which allows them to give birth to a normal child in 85% of the cases, whereas without treatment the success rate is only 37% of the pregnancies. When this therapy is applied in accurate conditions, its inocuousness seems well established. Another kind of this immunomodulator therapy has been reported: it uses unrelated donor leucocytes. Its efficiency seems to be similar to that of the husband's leucocyte injections.

Abortion, Habitual↗

[Immunologic abortion and its treatment by immunotherapy].

Recurrent spontaneous abortions in most cases, can be explained by classical abnormalities; but for some cases without etiology and consequently without appropriate therapy until a few years ago, there is hope a successful treatment, thanks to recent advances. Contrary to what was suspected in the past, during pregnancy, the mother is immunologically competent against the paternal antigens of the fetus; this competence is necessary for her to respond to the trophoblast paternal antigen stimulations and develop her immune tolerance. If, because of insufficient stimulation, the woman does not succeed in producing this tolerance, it is now possible to help her by vaccination with paternal lymphocytes, before she becomes pregnant. Our results confirm these data: Again, we observe a greater frequency of HLA antigen sharing in couples with recurrent spontaneous abortions (RSAs), especially at the DR locus, Women with three or more RSAs, produce fewer antibodies against their husbands HLA antigens than regular normal fertile women (none out of the 50 cases studied), Anti-paternal antibodies the specificity of which cannot be determined at the moment, are shown by means of the microlymphocytotoxicity test at 37 degrees C carried out on the paternal B lymphocytes. They appear with the cure of the abortive illness after treatment by paternal lymphocyte injections. In the control women who did not receive any immunotherapy, those who developed anti-paternal antibodies spontaneously had a new normal pregnancy; 57.2 of those who did not produce any anti-paternal antibodies aborted once more.

Abortion, Spontaneous↗

[Immunization against the ZWa (PLA1) platelet antigen: group at risk, prevention of complications. Apropos of 132 cases].

The identification of anti-ZWa (-PLA1) alloimmunisation is not very frequent. It can be observed in most perinatal alloimmune thrombocytopenias (PAT) and rare post transfusional purpuras (PTP). On the other hand, the clinical consequences of these immunisations are often dramatic, particularly for the foetuses for which there has been no prevention so far. The retrospective study of 132 cases, 123 PAT and 9 PTP, shows the possible irreversible complications for 18% of the newborns with PAT, but especially for 10% of the foetuses which will show PAT at birth. HLA markers are very useful to detect the people who are likely to develop an anti-PLA1 immunization for they are PLA1 negative and HLA DR3. Then, it becomes possible to prevent the complications of these immunisations. It is what we tried to do through the diagnosis and the treatment of PAT in 3 foetuses.

Antigens, Human Platelet↗

[Neonatal alloimmune thrombopenia. Clinical and biological study of 84 cases].

Eighty-four patients with neonatal alloimmune thrombocytopenia (NAT) were investigated clinically and by biological laboratory methods. The condition appeared at birth, usually as an isolated thrombocytopenic purpura, but in about 20% of the neonates the haemorrhagic syndrome was associated with signs of infection or with jaundice and hepatosplenomegaly. Considerable variations were observed in the severity of the purpura; in 3 cases the thrombocytopenia was clinically silent. Haemorrhagic brain lesions were present in 7% of the neonates, and severe neurological sequelae in 14 of the 59 children on long-term follow-up. The overall mortality rate was 9.2%. The PLA1 system was involved in 56 of the 59 families studied, with PLA1-negative mothers developing immunization against the foetus' PLA1 antigen. In 20% of these mothers the antibody was not demonstrable, and the diagnosis relied on the mother's phenotype and on a history of previous NAT. The strong association demonstrated between the HLA-DR3 antigen and the ability to develop anti-PLA1 antibodies is of extreme importance. It may be helpful to confirm the diagnosis in mothers without detectable anti-PLA1 antibodies and to identify mothers at risk of alloimmunization. Neurological sequelae, which were due to post-natal haemorrhage in at least 70% of the cases, could now be avoided by an early diagnosis, modern transfusional techniques and caesarian section. However, antenatal lesions cannot be avoided, except by preventive measures, yet to be developed, against alloimmunization or the cytopenic effect of the platelet antibody.

Blood Group Incompatibility↗