Progesterone induced blocking factor (PIBF) taken in early pregnancy predicts the pregnancy outcome in women undergoing in vitro fertilization procedure.

Earlier data suggest a relationship between PIBF concentrations and the outcome of pregnancy. The aim of the study was to compare serum and urine concentrations of PIBF in women with successful pregnancy after IVF with those of women without pregnancy after IVF procedure, and to evaluate the potential relation between PIBF and the outcome of pregnancy. Urine and serum were collected from 120 women, undergoing IVF. 87.5% of patients had primary infertility. 69.2% faced female causes of infertility: 10.8% tubal cause, 11.7% ovulation disorder, and 46.7% other causes of infertility. 30.8% of patients had male factor of infertility. Among non-pregnant women (42) mean concentrations of PIBF in urine and serum were significantly lower (15.8 ng/mL; 148.4 ng/mL) than in women with positive beta HCG value (78) (19.1 ng/mL; 225.9 ng/mL). In 49 patients pregnancy terminated with a term delivery, in 10 patients with pretem delivery, while in 19 patients the pregnancy terminated with a miscarriage. PIBF concentrations in urine (13.9 ± 2.8 ng/mL) and serum (124.6 ± 46.7 ng/mL) samples of women with miscarriage were significantly lower of those with preterm delivery (180.6 ± 54.4 ng/mL; 18.1 ± 4.4 ng/mL) and of those with term delivery (20.4 ± 8.5 ng/mL; 208.7 ± 114.3 ng/mL). Successful pregnancy after IVF procedure is predictable by measuring of urine and serum PIBF concentrations and could be important for predicting of early implantation and pregnancy outcome after IVF procedure and maybe to protect the risk pregnancy.

Lower Urinary and Serum Progesterone-Induced Blocking Factor in Women with Preterm Birth.

The aim of the study was to compare urine and serum concentrations of PIBF at 24-28 gestational weeks in women with preterm birth, with those of women who delivered at term and to evaluate the impact of PIBF on the outcome of pregnancy. Case-control study was performed in period from 1.6.2010-31.7.2013. Biological samples (urine and serum) were collected from 126 pregnant women. All biological samples were obtained at 24-28 gestation weeks. We measured PIBF concentration and compared women who delivered preterm and those who delivered at term. Thirteen of 126 pregnant women (10.3%) who were included in the study delivered preterm. Among women that actually delivered preterm, median concentrations of PIBF were significantly lower (12.3ng/ml; 101.3ng/ml) than in women who delivered at term (77.0ng/ml; 412.7ng/ml). The serum and urine 24-28 gestational weeks PIBF in those who delivered preterm were generally low from 24 to 37 gestational weeks, while the serum and urine PIBF concentration reached a peak in those delivering between 37-38 gestational weeks, even significantly different from those delivering at 39 to 40 and after 40 gestational weeks. Preterm birth may be predictable at 24-28 gestational week by lower than normal pregnancy PIBF values and measurement of PIBF concentration in biological fluids at that time may be of importance in clinical practice.

Changes of progesterone-induced blocking factor in patients after kidney transplantation.

The prediction of graft rejection can play an important part in graft survival. Analysis of immune reactions has shown that graft rejection shares mechanisms with recurrent abortions during pregnancy. Progesterone-induced blocking factor (PIBF), a mediator of progesterone that blocks natural killer cell activity in peripheral blood, produces antiabortive effects. The aim of this study was to examine the PIBF concentration in the urine of transplanted recipients. The study included 116 white adults (70 men and 46 women) of median age 49.3 years, who had undergone kidney transplantations. The median duration after transplantation was 3.46 years. The average period between renal disease and our measurement was 12.3 years, and the median interval between graft rejection and our study was 1.75 years. Urine samples were used to measure PIBF concentrations by an enzyme-linked immunsorbent assay. PIBF urinary concentrations decreased significantly in patients who experienced ≥1 rejection episode (31.8±2.2 ng/mL) compared with those without any episode (22.7±1.2 ng/ml; P<.01). Moreover, the urinary PIBF level was significantly lower among patients who had increased creatinine and urea nitrogen levels in blood samples (P<.05 and P<.01, respectively). Decreased PIBF values in kidney transplant patients followed previous rejection episodes. A close negative correlation was observed between urinary PIBF concentrations and blood levels of creatinine and urea nitrogen. These findings suggested that PIBF detection may predict graft rejection in transplant recipients.

Progesterone - induced blocking factor (PIBF) and Th(1)/Th(2) cytokine in women with threatened spontaneous abortion.

OBJECTIVE: The aim of this prospective study was to compare serum and urine concentrations of progesterone-induced blocking factor (PIBF) and serum concentrations of anti-inflammatory (IL10) and pro-inflammatory (IL6, TNFalpha, IFNgamma) cytokines of women with threatened spontaneous abortion with normal pregnancy and to evaluate the impact of PIBF on outcome of pregnancy. METHODS: A sample of 30 women with threatened spontaneous abortion (study group) and 20 healthy pregnant women (control group) between 6(th) and 24(th) gestational weeks was studied. Serum and urine PIBF, IL10 and IL6, TNFalpha, IFNgamma cytokine concentrations were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Five (16.7%) pregnancies in the study group ended missed abortion vs. none in the control group (P<0.05). Five (20%) threatened aborters delivered between 24(th) and 37(th) weeks of gestation, whereas two (10%) preterm deliveries occurred in the controls (P>0.05). PIBF concentrations in urine (19.5+/-12.9 ng/mL) and serum (214.4+/-120.6 of patients with threatened abortion were significantly lower than in healthy pregnant women (45.3+/-33.7 ng/mL and 357.3+/-159.9 ng/mL, respectively). Women with threatened abortion had significantly lower serum levels of anti-inflammatory cytokine, but levels of proinflammatory cytokines were higher in this group compared with healthy controls. CONCLUSIONS: Determination of progesteron-induced blocking factor level in body fluids in early pregnancy might be used for the diagnosis and prognosis of threatened abortion.

Human trophoblast cells express the immunomodulator progesterone-induced blocking factor.

Progesterone-induced blocking factor (PIBF) is an immunomoduatory factor with anti-abortive properties. In this study, we present evidence that PIBF is synthesized in the human placenta and determine its cellular source. Expression of PIBF was analysed with polyclonal rabbit anti-human PIBF antibodies against recombinant N-terminal 48kDa PIBF in first trimester and term placental tissues and in the choriocarcinoma cell line JAR by means of immunohistochemistry, confocal laser scanning microscopy of double immunofluorescence labelling, and Western blotting; RT-PCR was performed for analysis of PIBF mRNA in isolated trophoblast cells. PIBF protein is present in human first trimester and term placenta. Double immunofluorescence labelling localised PIBF to the extravillous cytotrophoblast. PIBF is also expressed heterogeneously by syncytiotrophoblast and part of the villous cytotrophoblast. Full-length PIBF mRNA encoded by exons 1-18 is present in isolated first trimester and term villous trophoblast and in the choriocarcinoma cell line JAR. The corresponding 90kDa protein is expressed by JAR cells, first trimester and term villous trophoblast cells. In addition, these cells express PIBF proteins of 50 and 34kDa. Trophoblast is a source of PIBF; its tissue distribution suggests a role both in systemic and local (decidual) immunoregulation.

Production and characterization of a novel monoclonal antibody against progesterone-induced blocking factor (PIBF).

Progesterone-induced blocking factor (PIBF) has been described as an active factor intimately involved in regulation of the immune response in pregnancy. It has been shown that PIBF biased the cytokine balance to Th2-type in pregnancy and inhibited the activity of NK cells. The biological roles of PIBF would be better defined if methods for its detection and measurement in biological fluids are available. However, so far, reliable antibodies have not been developed to be used as specific probes. A monoclonal antibody designated as MAB 3A6 was produced and characterized. MAB 3A6 reacts specifically with PIBF. It can detect this protein in biological fluids when tested by immunoblot and recognizes PIBF expressed on the surface of lymphocytes of pregnant women stimulated in vitro with progesterone. The characteristics of MAB 3A6 makes it the possible basis for development of a clinically applicable assay to assess the presence and concentration of PIBF in biological samples.

Progesterone-dependent immunomodulation.

The biological effects of progesterone are mediated by a 34-kDa protein named the progesterone-induced blocking factor (PIBF). PIBF, synthesized by lymphocytes of healthy pregnant women in the presence of progesterone, inhibits arachidonic acid release as well as NK activity, and modifies the cytokine balance. Within the cell the full-length PIBF is associated with the centrosome, while secretion of shorter forms is induced by activation of the cell. PIBF induces nuclear translocation of STAT6 as well as PKC phosphorylation and exerts a negative effect on STAT4 phosphorylation. The concentration of PIBF in pregnancy urine is related to the positive or negative outcome of pregnancy; furthermore, premature pregnancy termination is predictable by lower than normal pregnancy PIBF values. In vivo data suggest the biological importance of the above findings. Treatment of pregnant Balb/c mice with the antiprogesterone RU 486 results in an increased resorption rate, which is associated with the inability of spleen cells to produce PIBF. High resorption rates induced by progesterone receptor block as well as those due to high NK activity are corrected by simultaneous PIBF treatment.