New pre-conception immune biomarkers for clinical practice: interleukin-18, interleukin-15 and TWEAK on the endometrial side, G-CSF on the follicular side.
; ; et al
in Journal of Reproductive Immunology (2011), 88(2), 118-123
dentification of biomarkers of optimal uterine receptivity to the implanting embryo as well as biomarkers of oocyte competence would undoubtedly improve the efficiency of assisted reproductive technology ... [more ▼]
dentification of biomarkers of optimal uterine receptivity to the implanting embryo as well as biomarkers of oocyte competence would undoubtedly improve the efficiency of assisted reproductive technology (ART). Expression of IL-15 and IL-18 has been shown to be different in patients with failed implantation after IVF/ICSI compared with fertile controls and both correlate with local uNK (CD56+) recruitment and angiogenesis. Tumor necrosis factor weak inducer of apoptosis (TWEAK) has been described in mice as a potent early immune regulator able to protect the conceptus. The results of our studies in human suggest that TWEAK modulates the IL-18 related cytotoxicity of uNK cells. Quantification of IL-18, TWEAK and IL-15 mRNA expression by real-time PCR in endometrial tissue collected in mid-luteal phase of non-conception cycles allowed documentation of physiological events that occur at the time of uterine receptivity. Such information may be useful for the physician especially in patients where embryos fail to implant. Cytokine quantification may assist in understanding the mechanisms leading to repeated IVF/ICSI failure: either depletion of cytokines necessary for the apposition-adhesion, or an excess of cytokines leading to local cytotoxicity, may impair the implantation of the embryo. Other new data suggest that a pre-conception dialogue mediated by the oocyte and the follicular fluid and the oocyte may contribute to later implantation success. Follicular concentration of G-CSF appears as a useful biomarker of oocyte competence before fertilization. Moreover both in human and animal models, evidence of a role of the endometrium as a biosensor of the embryo is emerging. [less ▲]Detailed reference viewed: 48 (15 ULg)
An insight into normal and pathological pregnancies using large-scale microarrays: lessons from microarrays
; ; et al
in Journal of Reproductive Immunology (2011), 89(2), 163-72
In the introduction, we briefly recall old but classic evidence that there is no tolerance to paternal alloantigens in a first pregnancy. Therefore, we performed small- and large-scale microarrays in CBA ... [more ▼]
In the introduction, we briefly recall old but classic evidence that there is no tolerance to paternal alloantigens in a first pregnancy. Therefore, we performed small- and large-scale microarrays in CBA × DBA/2 and CBA × BALB/c combinations, recently described as a murine model for preeclampsia. Our results are in line with other data suggesting a very early deregulation of local immune vascular events rather than a break of immune tolerance. Other data presented at the Tioman 2010 Preeclampsia Workshop supporting this hypothesis are briefly summarised, as well as indications and caveats from a recent human microarray on implantation failure and recurrent pregnancy loss. [less ▲]Detailed reference viewed: 14 (3 ULg)
Performance evaluation of microbead and ELISA assays for follicular G-CSF: a non-invasive biomarker of oocyte developmental competence for embryo implantation.
; Munaut, Carine ; et al
in Journal of Reproductive Immunology (2010), 86(2), 126-32
G-CSF in individual follicular fluids correlates with the potential of the corresponding embryo to result in a live birth after transfer in IVF. To evaluate the requirements for routine follicular fluid G ... [more ▼]
G-CSF in individual follicular fluids correlates with the potential of the corresponding embryo to result in a live birth after transfer in IVF. To evaluate the requirements for routine follicular fluid G-CSF quantification, we compared follicular fluid G-CSF measurements made with two multiplexed microbead assays purchased from Bio-Rad Laboratories and R&D Systems, and a commercial G-CSF ELISA (R&D Systems). Individual follicular fluids (n=139) associated with transferred embryos were analysed to determine cytokine profile and the fate of each transferred embryo was recorded. The effect of multiplexing as well as comparison of the respective performances of the microbead assay with a flow cytometry assay was explored. Multivariable logistic regression analysis was performed and receiver operating characteristic (ROC) analysis was used to determine the performance and sensitivity/specificity of each method for individual follicular fluids. Covariate factors known to influence IVF outcome such as age, serum oestradiol and embryo score were systematically integrated in each analysis. The quantification of follicular fluid G-CSF using microbead assay methodologies, but not ELISA, yielded results showing the utility of follicular fluid G-CSF as a biomarker predictive of a successful delivery (Au(roc): 0.77 [0.68-0.84] (p=0.003) and 0.75 [0.66-0.82] (p=0.004) for Bio-Rad and R&D Systems microbead assays respectively), whereas follicular fluid G-CSF values quantified by ELISA were not predictive (Au(roc):0.61 [0.52-0.70] p=0.84). Microbead assay and flow cytometry appeared similarly efficient for quantifying follicular fluid G-CSF and multiplex versus single-plex assays did not influence the reliability of quantification. [less ▲]Detailed reference viewed: 45 (16 ULg)
Human Chorionic Gonadotropin: a hormone with immunological and angiogenic properties.
; Gridelet, Virginie ; Berndt, Sarah et al
in Journal of Reproductive Immunology (2010), 85(1), 93-8
The success of implantation depends on a receptive endometrium, a normal blastocyst and synchronized cross-talk at the maternal–fetal interface. The progression of pregnancy then requires immunological ... [more ▼]
The success of implantation depends on a receptive endometrium, a normal blastocyst and synchronized cross-talk at the maternal–fetal interface. The progression of pregnancy then requires immunological tolerance which allows conceptus survival. A cascade of cytokines mediates this dialogue and is crucial in the cross-talk between the immune and endocrine systems. The first known human embryo-derived signal is chorionic gonadotropin (hCG) by which the embryo profoundly influences immunological tolerance and angiogenesis at the maternal–fetal interface. hCG levels coincide with the development of trophoblast tolerance. Indeed, it increases the number of uterine natural killer cells that play a key role in the establishment of pregnancy. hCG also intervenes in the development of local immune tolerance through the cellular system of apoptosis via Fas/Fas-Ligand. It modulates the Th1/Th2 balance and acts on complement C3 and C4A/B factors modulating decidual immunity. The transient tolerance evident during gestation is at least partially achieved via the presence of regulatory T cells which are attracted by hCG at the fetal–maternal interface. Finally, hCG treatment of activated dendritic cells results in an up-regulation of MHC class II, IL-10 and IDO expression, reducing the ability to stimulate T cell proliferation. Successful implantation requires an extensive endometrial angiogenesis in the implantation site. Recent data demonstrate angiogenic effects of hCG via its interaction with endometrial and endothelial LH/hCG receptors. Our review focuses on these functions of hCG, giving new insight into the endocrine–immune dialogue that exists between the conceptus and immune cells within the receptive endometrium at the time of implantation. [less ▲]Detailed reference viewed: 56 (18 ULg)
Dysregulation of anti-angiogenic agents (sFlt-1, PLGF, and sEndoglin) in preeclampsia--a step forward but not the definitive answer
Foidart, Jean-Michel ; Schaaps, Jean-Pierre ; Chantraine, Frédéric et al
in Journal of Reproductive Immunology (2009), 82(2), 106-11
Preeclampsia (PE) is a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, which resolves on placental delivery. It is thought to be the consequence of impaired placentation ... [more ▼]
Preeclampsia (PE) is a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, which resolves on placental delivery. It is thought to be the consequence of impaired placentation due to inadequate trophoblastic invasion of the maternal spiral arteries. In PE the maternal plasma concentration of free vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) is decreased whereas the concentration of soluble fms-like tyrosine kinase-1 (sFlt-1) and of soluble endoglin (sEng) is increased. These soluble receptors may bind VEGF, PLGF and TGFβ1 and TGFβ3 in the maternal circulation, causing endothelial dysfunction in many maternal tissues. Hence there is a view that the pathogenesis is more or less clarified. According to the vascular theory, poor placentation leads to poor uteroplacental perfusion and hypoxia, which stimulates sFlt-1 and sEng production causing the maternal syndrome. This assumption has been recently challenged. The role of hypoxia as the main stimulus for release of sFlt-1 has been questioned and the role of inflammatory mechanisms has been emphasized. According to this inflammatory theory, poor placentation may predispose more to placental oxidative stress than hypoxia and endothelial dysfunction may be part of a broader disorder of systemic inflammation. Finally, the recent demonstration of activating auto-antibodies to the angiotensin 1 receptor that experimentally play a major pathogenic role in PE further suggests a pleiotropism of aetiologies for this condition. The purpose of this review is to critically evaluate the recent hypotheses and their possible insights on early diagnosis, prevention and treatment. [less ▲]Detailed reference viewed: 97 (7 ULg)
The human tumor-associated antigen RCAS1 in pregnancies complicated by pre-eclampsia.
Tskitishvili, Ekaterine ; ; et al
in Journal of Reproductive Immunology (2008), 77(1), 100-8
The human tumor-associated antigen RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is considered to play a role in the escape of tumor cells from immune surveillance and, at the same time ... [more ▼]
The human tumor-associated antigen RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is considered to play a role in the escape of tumor cells from immune surveillance and, at the same time, participates in the inhibition of the maternal immune response during pregnancy. The aim of our study was to investigate the expression of tumor-associated RCAS1 protein in the placenta and amniotic membranes and to assess and compare its concentration in amniotic fluid, maternal and cord blood sera in pregnancies complicated by pre-eclampsia. Samples were obtained from women with pre-eclampsia (N=9), pre-eclampsia with IUGR (N=4), normotensive IUGR (N=7) and healthy term controls (N=25) after delivery. Placentas were studied by immunohistochemistry, Western blot analysis and real-time (RT)-PCR. For assessment of RCAS1 protein concentrations in biological fluids, ELISA was performed. RCAS1 mRNA expression in the placentas of pre-eclamptic patients was significantly lower than in controls (p<0.01). The maternal blood serum RCAS1 protein concentration in the pre-eclampsia cases was also significantly lower than in controls (p=0.0207). The other study groups did not differ significantly. This study reveals the possible role of the RCAS1 protein in the development of pre-eclampsia through an immunological pathway. [less ▲]Detailed reference viewed: 30 (9 ULg)
Significance of soluble HLA-G detection in follicular fluids and embryo supernatants in IVF/ICSI cycles
Lédée, Nathalie ; Thonon, Fabienne ; PERRIER d'HAUTERIVE, Sophie et al
in Journal of Reproductive Immunology (2007, August), 75(1), 11Detailed reference viewed: 15 (5 ULg)