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Lymphocyte immunization therapy: Role in Repeated Miscarriages & Implantation Failure
Abstracts of poster session / Journal of Reproductive Immunology 115 (2016) 56–70
P1-24
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Isolated IgGs from sera of recurrent miscarriage (RM) patients with anti-trophoblast antibodies suppress the expression of human Chorionic Gonadotropin (hCG) and stimulated the expression of Plaminogen-Activator-Inhibitor Type 1 (PAI-1) in JEG-3 cells in
Maternal and neonatal Fms-like tyrosine kinase 3 ligand (Flt-3L) levels: Modulation of neonatal immune maturity and childhood immune diseases
Yao Ye, Marianne Vogel, Petra Burger, Christian J. Thaler, Nina Rogenhofer, Udo Jeschke, Sven Mahner, Viktoria von Schönfeldt Division of Gynecological Endocrinology and Reproductive Medicine, Department of Gynecology and Obstetrics, Ludwig-Maximilian University of Munich, Germany Background: Anti-trophoblast antibodies (ATAB) are significantly more prevalent in recurrent miscarriage (RM) patients as compared with controls. To date, it remains to be elucidated by which mechanism ATAB may have effect on early gestation. Based on the previous results we investigated whether Immunoglobulin Gs (IgGs) isolated from sera of RM patients effect hCG expression in vitro using the choricarcinoma cell line JEG-3. Material and methods: IgGs were isolated and concentrated from sera of RM patients with and without ATAB and added to culture media of JEG-3 cells in various concentrations (0 g/mL, 5 g/mL, 50 g/mL). IgGs isolated accordingly from the ATABnegative group served as controls. Culture supernatants were collected at different timepoints (12 h, 24 h, 36 h). The expression levels of hCG and of PAI-1 were analyzed by ELISA Results: The isolated IgGs of ATAB-positive patients suppressed hCG expression of JEG-3 cells for 12 h of incubation in a dosedependant manner (P = 0.043, 50 g/mL). IgGs of ATAB-positive patients also exacerbated PAI-1 expression levels compared to controls (P = 0.027). Discussion: Isolated IgGs of ATAB-positive RM patients suppress hCG expression while stimulating PAI-1 expression in vitro. PAI-1 functions as the main inhibitor of fibrinolysis. In RM patients, increased PAI-1 expression might contribute to elevated intervillous fibrin deposition and lower placental perfusion in patients with ATAB thus resulting in recurrent miscarriages. http://dx.doi.org/10.1016/j.jri.2016.04.195 P1-25 Lymphocyte immunization therapy: Role in Repeated Miscarriages & Implantation Failure Mohan K. Raut, Mugdha M. Raut Immunotherapy Centre for Prevention of Repeated Miscarriages (ICPRM), Mumbai, India Immunology plays a very important role in Repeated Miscarriages, Implantation Failure & Unexplained Infertility. 125 couples with these problems were investigated at ICPRM, Mumbai, India, for immunological factor. Levels of peripheral NK cells (CD3 and CD16+56), endometrial NK cells (CD57) and serum TNF alpha were estimated after ruling out other known causes. 95 couples were given lymphocyte immunization therapy (LIT) using husband’s lymphocytes. There are 52 pregnancies so far after the therapy (16 delivered and 30 ongoing). There were 6 miscarriages after LIT. This shows that LIT is beneficial in Repeated Miscarriages & Implantation Failure. http://dx.doi.org/10.1016/j.jri.2016.04.196
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Anke Diemert, Justine Tanoey, Heiko Becher, Petra C. Arck Department for Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Germany Background: Flt-3L activates the proliferation and maturation of hematopoietic progenitor cells, hereby inducing the generation of immune cell subsets including T cells. It is detectable in peripheral and cord blood but normal value ranges or its role for fetal immune maturation are unknown. The immune system largely develops prior to birth and hematopoiesis arises from stem cell reservoirs during fetal development. We investigated whether maternal Flt-3L levels can predict cord blood Flt-3L levels and immune maturation at birth. Method: 79 mother–child pairs from the prospective birth cohort PRINCE (PRenatal DetermINation of Children’s HEalth) were analyzed once every trimester plus cord blood at birth. Maternal data include age, BMI, and levels of Flt-3L. Neonatal data includes gestational age, sex and weight. Cord blood examination includes Flt-3L level and frequency of immune cell subsets. Data was analyzed using correlation analysis and linear regression. Results: Mean maternal Flt-3L levels increase during pregnancy by 8%. Cord blood Flt-3L levels decrease in relation to gestational age at birth (ˇ = −4.95, p < 0.01). Cord blood Flt-3L, in contrast to maternal Flt-3L, is positively correlated with the frequency of FoxP3+ CD25+ CD4+ regulatory T cells and mature CD45+ CD34+ hematopoetic stem cells expressing CD135. Conclusion: Cord blood Flt-3L levels are correlated with regulatory T cells at birth and may be an additional indicator for childhood allergies. http://dx.doi.org/10.1016/j.jri.2016.04.197 P1-27 Maternal KIR-B haplotype in combination with fetal HLA-C2 is associated with pregnancy acute atherosis in the decidua basalis Guro M. Johnsen, Gro L. Størvold, Jos J.M. Drabbels, Geert W. Haasnoot, Michael Eikmans, Patji Alnæs-Katjavivi, Sicco Scherjon, Christopher W. Redman, Frans Claas, Anne Catherine Staff Institute for Clinical Medicine, Faculty of Medicine, University of Oslo & Department of Obstetrics and Gynaecology, Oslo University Hospital, Norway Uteroplacental acute atherosis (AA) is similar to early atherosclerotic lesions. AA lesions are most prevalent at the tip of spiral arteries in the decidua basalis, the tissue underlying the placenta and the main fetal-maternal immunological junction in pregnancy. Interaction of fetal HLA-C on placental trophoblasts with killer-immunoglobulin-like-receptors (KIR) on maternal NKcells is important in transforming the spiral arteries into wide vessels essential for placental growth. We hypothesized that fetalmaternal HLA mismatches, and specific fetal HLA and maternal KIR haplotype combinations are associated with AA. Paired maternal and fetal blood samples were collected at Oslo University Hospital from 218 pregnancies. All pregnancies were
P1-24
P1-26
Isolated IgGs from sera of recurrent miscarriage (RM) patients with anti-trophoblast antibodies suppress the expression of human Chorionic Gonadotropin (hCG) and stimulated the expression of Plaminogen-Activator-Inhibitor Type 1 (PAI-1) in JEG-3 cells in
Maternal and neonatal Fms-like tyrosine kinase 3 ligand (Flt-3L) levels: Modulation of neonatal immune maturity and childhood immune diseases
Yao Ye, Marianne Vogel, Petra Burger, Christian J. Thaler, Nina Rogenhofer, Udo Jeschke, Sven Mahner, Viktoria von Schönfeldt Division of Gynecological Endocrinology and Reproductive Medicine, Department of Gynecology and Obstetrics, Ludwig-Maximilian University of Munich, Germany Background: Anti-trophoblast antibodies (ATAB) are significantly more prevalent in recurrent miscarriage (RM) patients as compared with controls. To date, it remains to be elucidated by which mechanism ATAB may have effect on early gestation. Based on the previous results we investigated whether Immunoglobulin Gs (IgGs) isolated from sera of RM patients effect hCG expression in vitro using the choricarcinoma cell line JEG-3. Material and methods: IgGs were isolated and concentrated from sera of RM patients with and without ATAB and added to culture media of JEG-3 cells in various concentrations (0 g/mL, 5 g/mL, 50 g/mL). IgGs isolated accordingly from the ATABnegative group served as controls. Culture supernatants were collected at different timepoints (12 h, 24 h, 36 h). The expression levels of hCG and of PAI-1 were analyzed by ELISA Results: The isolated IgGs of ATAB-positive patients suppressed hCG expression of JEG-3 cells for 12 h of incubation in a dosedependant manner (P = 0.043, 50 g/mL). IgGs of ATAB-positive patients also exacerbated PAI-1 expression levels compared to controls (P = 0.027). Discussion: Isolated IgGs of ATAB-positive RM patients suppress hCG expression while stimulating PAI-1 expression in vitro. PAI-1 functions as the main inhibitor of fibrinolysis. In RM patients, increased PAI-1 expression might contribute to elevated intervillous fibrin deposition and lower placental perfusion in patients with ATAB thus resulting in recurrent miscarriages. http://dx.doi.org/10.1016/j.jri.2016.04.195 P1-25 Lymphocyte immunization therapy: Role in Repeated Miscarriages & Implantation Failure Mohan K. Raut, Mugdha M. Raut Immunotherapy Centre for Prevention of Repeated Miscarriages (ICPRM), Mumbai, India Immunology plays a very important role in Repeated Miscarriages, Implantation Failure & Unexplained Infertility. 125 couples with these problems were investigated at ICPRM, Mumbai, India, for immunological factor. Levels of peripheral NK cells (CD3 and CD16+56), endometrial NK cells (CD57) and serum TNF alpha were estimated after ruling out other known causes. 95 couples were given lymphocyte immunization therapy (LIT) using husband’s lymphocytes. There are 52 pregnancies so far after the therapy (16 delivered and 30 ongoing). There were 6 miscarriages after LIT. This shows that LIT is beneficial in Repeated Miscarriages & Implantation Failure. http://dx.doi.org/10.1016/j.jri.2016.04.196
63
Anke Diemert, Justine Tanoey, Heiko Becher, Petra C. Arck Department for Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Germany Background: Flt-3L activates the proliferation and maturation of hematopoietic progenitor cells, hereby inducing the generation of immune cell subsets including T cells. It is detectable in peripheral and cord blood but normal value ranges or its role for fetal immune maturation are unknown. The immune system largely develops prior to birth and hematopoiesis arises from stem cell reservoirs during fetal development. We investigated whether maternal Flt-3L levels can predict cord blood Flt-3L levels and immune maturation at birth. Method: 79 mother–child pairs from the prospective birth cohort PRINCE (PRenatal DetermINation of Children’s HEalth) were analyzed once every trimester plus cord blood at birth. Maternal data include age, BMI, and levels of Flt-3L. Neonatal data includes gestational age, sex and weight. Cord blood examination includes Flt-3L level and frequency of immune cell subsets. Data was analyzed using correlation analysis and linear regression. Results: Mean maternal Flt-3L levels increase during pregnancy by 8%. Cord blood Flt-3L levels decrease in relation to gestational age at birth (ˇ = −4.95, p < 0.01). Cord blood Flt-3L, in contrast to maternal Flt-3L, is positively correlated with the frequency of FoxP3+ CD25+ CD4+ regulatory T cells and mature CD45+ CD34+ hematopoetic stem cells expressing CD135. Conclusion: Cord blood Flt-3L levels are correlated with regulatory T cells at birth and may be an additional indicator for childhood allergies. http://dx.doi.org/10.1016/j.jri.2016.04.197 P1-27 Maternal KIR-B haplotype in combination with fetal HLA-C2 is associated with pregnancy acute atherosis in the decidua basalis Guro M. Johnsen, Gro L. Størvold, Jos J.M. Drabbels, Geert W. Haasnoot, Michael Eikmans, Patji Alnæs-Katjavivi, Sicco Scherjon, Christopher W. Redman, Frans Claas, Anne Catherine Staff Institute for Clinical Medicine, Faculty of Medicine, University of Oslo & Department of Obstetrics and Gynaecology, Oslo University Hospital, Norway Uteroplacental acute atherosis (AA) is similar to early atherosclerotic lesions. AA lesions are most prevalent at the tip of spiral arteries in the decidua basalis, the tissue underlying the placenta and the main fetal-maternal immunological junction in pregnancy. Interaction of fetal HLA-C on placental trophoblasts with killer-immunoglobulin-like-receptors (KIR) on maternal NKcells is important in transforming the spiral arteries into wide vessels essential for placental growth. We hypothesized that fetalmaternal HLA mismatches, and specific fetal HLA and maternal KIR haplotype combinations are associated with AA. Paired maternal and fetal blood samples were collected at Oslo University Hospital from 218 pregnancies. All pregnancies were