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Biomedical subjects

A E Beer

Publications and source records attributed to A E Beer.

At least 37 records · Page 2Linked to original sources
PubMed1995

Intravenous immunoglobulin infusion therapy in women with recurrent spontaneous abortions of immune etiologies.

We have investigated clinical effectiveness of intravenous immunoglobulin G infusion (IVIg) on antiphospholipid antibody titers in five women with evidence of antiphospholipid antibody-associated recurrent spontaneous abortions and one with antinuclear antibody who became refractory to conventional autoimmune treatment during pregnancy and experienced pregnancy complications. Three women developed intrauterine growth retardation and three had complicated twin pregnancies with rising autoantibody titers. Antiphospholipid antibody and antinuclear antibody titers were tested pre and 2 weeks after each IVIg infusion. We report that: (i) IgG antiphospholipid antibody titers were significantly suppressed after each IVIg infusion (P < 0.05); (ii) IgM antiphospholipid antibody titers were also significantly suppressed after each IVIg infusion (P < 0.0001); (iii) decreased titers of autoantibodies paralleled increased levels of maternal IgG which lasted for at least 30 days; the autoantibodies showed a definite rise again prior to the next infusion; (iv) antinuclear antibody titers were effectively suppressed; and (v) rising autoantibody titers combined clinical manifestation of intrauterine growth retardation and women with complicated twin pregnancies. We conclude that IVIg infusion effectively suppresses IgM and IgG autoantibodies to phospholipids and antinuclear antibody in autoimmune women with a history of recurrent spontaneous abortions and refractory to conventional anticoagulation or immunosuppressive treatment.

Abortion, Habitual↗
PubMed1995

Up-regulated expression of CD56+, CD56+/CD16+, and CD19+ cells in peripheral blood lymphocytes in pregnant women with recurrent pregnancy losses.

PROBLEM: To analyze immunophenotypic profiles of peripheral blood and humoral autoimmune responses in women with a history of recurrent spontaneous abortions (RSA). METHOD: Peripheral blood lymphocyte subsets by flow cytometry and autoantibodies to phospholipids and nuclear components by ELISA were measured in nonpregnant and pregnant women with RSA of unknown etiology. Thirty-five pregnant and eighty-one nonpregnant women with RSA were studied. Seventeen nonpregnant and twenty-two pregnant normal controls were included. RESULTS: Natural killer (NK) cells (CD56+) were significantly elevated in nonpregnant women with RSA as compared with nonpregnant controls. Pregnant women with RSA demonstrated significantly increased NK (CD56+, CD56+/CD16+) and B cells (CD19+) as compared with pregnant controls. Women who miscarried the index pregnancy demonstrated significantly lower CD3+ cells in comparison with normal controls. Women with RSA and antiphospholipid antibodies showed significantly elevated NK cells when compared with women without antiphospholipid antibodies. Women with autoantibodies to nuclear components demonstrated significantly elevated CD19+/CD5+ cells when compared to women without autoantibodies to nuclear components. CONCLUSIONS: Women with RSA demonstrate an abnormal cellular immune response by increasing peripheral natural killer cells and B cells as compared with normal controls.

Abortion, Habitual↗
PubMed1994

Expression of a membrane form of the pregnancy-associated protein TJ6 on lymphocytes.

TJ6 is a novel protein which has immunosuppressive activity and may have a functional role in fetal allograft survival during pregnancy. Initial studies indicated that when mice were treated with an anti-TJ6 binding mAb early in pregnancy, the pregnancies were completely ablated and that TJ6 expression is enhanced dramatically during pregnancy. In addition we have cloned the cDNA for TJ6 which encodes a possible transmembrane domain that may include six to seven transmembrane regions. Therefore, we examined TJ6 expression on PBL of pregnant and non-pregnant women and found that TJ6 is expressed primarily on CD19+ B cells from pregnant but not nonpregnant women. TJ6 was not expressed on CD3+ lymphocytes from either group but was expressed on CD56+ cells from a small population of pregnant women which preliminary data indicate may correlate with the occurrence of spontaneous abortion in these women. Here we also show that TJ6 transcripts are highly expressed in the developing fetoplacental unit as well as in the developing thymus. We also begin to characterize the expression of TJ6 isoforms in an acute lymphocytic leukemia cell line (SB), murine thymus, and the developing murine fetoplacental unit, as well as the expression of a membrane form of TJ6 present on human lymphocytes during pregnancy. All of these cells and tissues expressed TJ6 proteins which were smaller than predicted based on either the cDNA sequence or the in vitro translation even though they expressed mRNA similar in size. The TJ6 isoforms varied in size from the 45-kDa isoform in SB cells to the 52-kDa isoform of the fetoplacental unit to a 70-kDa isoform in murine thymus. Flow cytometric analysis also demonstrated that similar to the CD19+ B cells from pregnant women, TJ6 is expressed on the surface of SB cells.

Antigens, CD↗
PubMed1994

Down-regulation of maternal antiphospholipid antibodies during early pregnancy and pregnancy outcome.

OBJECTIVE: We investigated the hypothesis that maternal autoimmune responses to phospholipid antigens measured before and during pregnancy are not related to successful pregnancy outcome. STUDY DESIGN: One hundred twenty-three women with recurrent spontaneous abortions were serially tested for antiphospholipid antibodies during their pregnancies. RESULTS: In 72 women with recurrent spontaneous abortions and without antiphospholipid antibodies before the pregnancy, the incidence of antiphospholipid antibody production at the time of pregnancy termination was significantly higher in those who miscarried the index pregnancy than those who were delivered of a live-born infant. In 51 antiphospholipid antibody-positive women with recurrent spontaneous abortions there were dramatic increases in titers of anticardiolipin antibody and antiphosphatidylserine antibody in those who miscarried the index pregnancy (p < 0.005). In women who were delivered of a live-born infant, the titers remained stable or decreased during pregnancy. CONCLUSIONS: Down-regulation of antiphospholipid antibody production during early pregnancy is associated with favorable pregnancy outcome.

Abortion, Habitual↗
PubMed1994

Decidual-trophoblast interactions: decidual lymphoid cell function in normal, anembryonic, missed abortion and ectopic human pregnancy.

This study was designed to investigate the consequences of decidua-trophoblast interactions on the phenotype, spontaneous and induced proliferation and immunoregulatory potential of decidual leukocytes in normal pregnancies (NP), anembryonic pregnancies (AP), missed abortions (MA) and ectopic pregnancies (EP). Spontaneous proliferation of decidual non-adherent cells (NAD) from pregnancies with viable trophoblast inside the uterus is significantly higher than proliferation of peripheral blood lymphocytes (PBL) from the same groups (P < 0.001 for NP; P < 0.05 for AP). Spontaneous proliferation of decidual NAD cells from NP was higher (P < 0.001) when compared with AP and EP. The induced (PHA and Con A) responses of PBL from women with normal and pathological pregnancies were significantly higher than that of decidual NAD cells (P < 0.001). Higher proliferation of NAD decidual cells was obtained when Con A-stimulated NP were compared with MA and EP (P < 0.01). The interaction of viable trophoblast with intrauterine decidua appears to be a prerequisite for the activation of NAD suppressor cells, since NAD cells from MA produced stimulation instead of suppression, and NAD cells from EP had no suppressive effect. On the contrary, both NAD and adherent (AD) decidual leukocytes from NP and AP produced very strong suppression of PHA or alloantigen-induced PBL proliferation. The contact between trophoblast and AD decidual leukocytes is not necessary for their suppressive function, since even higher suppression is obtained with the cells from ectopic pregnancies.

Abortion, Missed↗
PubMed1993

Characterization of antibodies induced by paternal lymphocyte immunization in couples with recurrent spontaneous abortion.

This study was designed to identify and characterize the allo- and autoantibodies induced following successful paternal lymphocyte immunization to prevent recurrent spontaneous abortion. Firstly the titers of maternal anti-paternal antibodies in women with successful pregnancies as determined by the flow cytometry crossmatch (FCXM) were highly variable; however, in all cases, the initial pre-immunization titers were negative and the post-immunization titers were positive by the FCXM in successfully treated women. Secondly, the specificities of maternal alloantibodies to paternal HLA antigens (immunogen) were evaluated. No all predicted antibodies to mismatched paternal HLA antigens were found by microlymphocytotoxicity (MCX) assays and the specificities varied. Thirdly, antibodies in post- but not preimmunization sera reacted with two lymphoid cell lines, SupT1 and SB; in addition, the rise and fall of the titers of these sera with paternal cells seemed to be reflected with the cell lines by the FCXM. Fourthly, autoantibodies to activated lymphocytes were detected and seemed to correlate with successful immunization since women who had another abortion following immunotherapy lacked these autoantibodies. These findings suggest that the antibody response following successful immunotherapy is complex and needs to be studied further to understand the mechanism of this treatment.

Abortion, Habitual↗
PubMed1993

Antibodies to phospholipids and nuclear antigens in non-pregnant women with unexplained spontaneous recurrent abortions.

In a collaborative study of 73 non-pregnant Kuwaiti women with unexplained spontaneous recurrent abortion (RSA), 30 control healthy non-pregnant multiparous Kuwaiti women and 20 North American women who received elective abortion(s), autoantibodies to 6 phospholipids and 9 nuclear antigens were measured. Women with recurrent spontaneous abortions demonstrated 3 times higher incidence of antibodies to phospholipids (30.1%) than controls (10% each) (P = 0.029). The incidence of both IgM and IgA class antiphospholipid antibodies were significantly higher than those of controls. The incidence of antibodies to cardiolipin in women with recurrent spontaneous abortions (12.3%) was significantly higher than those of controls (P = 0.035) and incidence of IgM but not IgG anticardiolipin antibody was significantly higher in women with RSAs than in controls (P = 0.053). The incidences of anti-polyinosinic acid (P = 0.035) and anti-histone 1 antibody (P = 0.052) were significantly higher in women with recurrent spontaneous abortions than controls. There was no significant difference in the incidence of autoantibodies between primary and secondary aborters. However, women with a history of second trimester abortions showed a higher incidence of antiphospholipid antibodies than women with first trimester abortions only. Recurrent spontaneous abortion is associated with autoantibodies to phospholipid epitopes including IgA antiphospholipid antibodies.

Abortion, Habitual↗
PubMed1992

Reproductive outcome in women with recurrent spontaneous abortions of alloimmune and autoimmune causes: preconception versus postconception treatment.

OBJECTIVES: The null hypothesis is that treatment of women with recurrent spontaneous abortions with anticoagulation and immunosuppression will not increase the reproductive outcome if it is started preconceptionally. STUDY DESIGN: Ninety-four women with recurrent spontaneous abortion with autoimmune abnormalities comprised the study group. Group I began autoimmune therapy 48 hours after ovulation: heparin 5000 U twice daily, aspirin 80 mg daily, and prednisone 5 mg twice daily, with an increase to 10 mg twice daily when pregnant. Group II started the same medication after a positive pregnancy test. Group III received no medication. Controls were 19 women with no autoimmune abnormalities. The frequency of reproductive outcome was subject to multiple comparison by the Duncan test. RESULTS: The percentages of live-born children in groups I, II, and III were 74%, 44%, and 11%, respectively. CONCLUSIONS: Preconception diagnostic work-up and treatment of autoimmune abnormalities in women with histories of recurrent spontaneous abortion is advocated.

Abortion, Habitual↗
PubMed1992

Autoantibodies in women with primary recurrent spontaneous abortion of unknown etiology.

A group of 153 women with 3 or more recurrent spontaneous abortions (RSAs) with unknown etiology and 90 normal multigravida controls were evaluated for antibodies to phospholipids and nuclear antigens. We demonstrate that women with recurrent spontaneous abortions showed significantly higher incidence of antibodies to phospholipids than normal multigravida controls. In contrast, the incidence of antibodies to polynucleotides and histones was not different between these two groups. These findings suggest that antiphospholipid antibodies are either epiphenomena or causally related to recurrent spontaneous abortions.

Abortion, Habitual↗
PubMed1991

The alloantibody response of pregnant women and its suppression by soluble HLA antigens and anti-idiotypic antibodies.

The aim of this study was to investigate the time course of maternal allosensitization to fetal HLA antigens during normal human pregnancy and to explore mechanisms of suppression of anti-HLA alloantibodies. We found that the mother produces antibodies against some but not all of the mismatched HLA antigens of the fetus as early as the 8th week of pregnancy. These antibodies (Ab1), however, are often complexed with soluble HLA alloantigens and become detectable when immune complexes are dissociated. Soluble HLA antigens of fetal origin are present in the maternal circulation throughout the entire pregnancy beginning at 8 weeks. In some women the production of anti-anti-HLA antibodies (Ab2) became evident as early as the first trimester, while in others Ab2 was documented during the second or third trimester. Analysis of antibody specificity showed that some healthy primipara develop antibodies reactive with self HLA antigens. Although the allo- and autoantibody responses appear to be modulated by soluble HLA antigens, cyclic variations in the level of alloantibodies, as well as the mother's selective response to some, but not all, paternal HLA antigens, are best explained by the development of anti-idiotypic antibodies.

Antibodies, Anti-Idiotypic↗
PubMed1991

Patterns of anti-phospholipid antibody specificities.

To determine the importance of assaying for anti-phospholipid (PL) antibodies other than anti-cardiolipin antibodies in patients with putative anti-phospholipid antibody syndrome (APA), 1,513 serum samples from over 399 patients with the potential for thromboembolic disease were tested for IgM, IgG or IgA class antibodies to the following phospholipids: cardiolipin, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol and phosphatidic acid. Non-specific binding was subtracted from total binding of antibodies to each PL to eliminate false positive ELISA results. Only patients whose sera contained antibody levels which were greater than three standard deviations above the means were considered positive. Patients who were positive for anti-PL antibody had antibodies to at least one of six phospholipids tested. Approximately 60% of the positive samples contained antibodies to a phospholipid other than cardiolipin. For IgG class, antibodies to phosphatidylserine were the most prevalent followed by antibodies to phosphatidylethanolamine and cardiolipin. These findings indicate that anti-phospholipid antibody analysis should be performed for more than anti-cardiolipin antibody to detect patients with APA.

Abortion, Habitual↗
PubMed1989

Analysis of anti-lymphocyte antibodies by flow cytometry or microlymphocytotoxicity in women with recurrent spontaneous abortions immunized with paternal leukocytes.

The identification of anti-lymphocyte antibodies was investigated in women with a history of recurrent spontaneous abortions who received leukocyte immunization treatment. The antibodies were detected by two-color flow cytometric analysis (FCMX) and by microlymphocytotoxicity (MCX). Twice the number of positive patients (women who had been immunized with paternal leukocytes and produced antilymphocyte antibodies) could be identified by flow cytometry versus a standard microcytotoxicity assay (66 versus 33%). In addition, when mixed lymphocyte culture assays were performed to determine if serum blocking factors had been induced, those couples who were positive by FCMX showed inhibition of the mixed lymphocyte culture responses in contrast to most FCMX negative patients who did not. Thus, the sensitivity of the FCMX and its rapidity makes it an alternative to the mixed lymphocyte culture assay for assessing immunotherapy in women with recurrent spontaneous abortions.

Abortion, Habitual↗
PubMed1987

Immunoglobulin therapy for autoimmune thrombocytopenia purpura during pregnancy. A report of two cases.

High-dose, intravenous immunoglobulin therapy may be effective in elevating low platelet counts in nonpregnant patients with autoimmune thrombocytopenia purpura (ATP). We used immunoglobulin successfully on two pregnant women with ATP who had been refractory to high-dose corticosteroid therapy. The 5-day infusions were started at 12 and 29 weeks' gestation, and the subsequent uncomplicated vaginal deliveries occurred after the shortest reported interval (8 days) and longest (28 weeks) following a single immunoglobulin infusion. A splenectomy was avoided, and no adverse maternal or neonatal effects were apparent.

Adult↗
PubMed1986

Circulating antisperm antibodies in recurrently aborting women.

One hundred seventy-three women with a history of three or more recurrent consecutive abortions were analyzed for circulating antisperm antibodies with a radiolabeled antiglobulin assay (RAA), a modified enzyme-linked immunosorbent assay (ELISA), a tray agglutination test (TAT), and a sperm immobilization test (SIT). No pregnancies were subsequently gestated to term in women who were antisperm antibody-positive unless they were inoculated with their husband's leukocytes as treatment for an immune basis (not related to antisperm antibodies) for their recurrent abortions. In women with an immune basis for their recurrent abortions, immunization with leukocytes from their male partners increased the ability of these women previously aborting their fetuses to carry their fetuses to term, even if they had positive results in the ELISA, TAT, and SIT; women with positive results in the RAA continued to abort subsequent pregnancies, despite leukocyte immunization. Immunization of antisperm antibody-positive women with their partner's leukocytes did not incite or increase the antisperm antibody titer, with any of the assay techniques.

Abortion, Spontaneous↗