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Natural killer cell activity in women with recurrent miscarriage
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Abstracts / Journal of Reproductive Immunology 118 (2016) 109–141
HIVIg was applied for 69 women with histories of four or more consecutive RM of unexplained etiology. The live birth rate was 89.3% and pregnancy complications such as premature delivery (18%), fetal growth restriction (12%) and cleft lip (in one case) were observed, while severe adverse effects were not observed in women. 60gIVIg was applied for 14 women with history of six or more RM of unexplained etiology between 2010 and 2013. The live birth rate was 30.8%, so significant increase in the live birth rate was not observed with 60gIVIg. The HIVIg may be effective for RM of unexplained etiology, whereas the 60gIVIg was not effective for RM. A randomized double blind placebo control study of HIVIg for RM of unexplained etiology is ongoing in Japan. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.067 59 Natural killer cell activity in women with recurrent miscarriage Yasuhiko Ebina ∗ , Yukari Nishino, Masashi Deguchi, Yoko Maesawa, Yuki Nakajima, Hideto Yamada Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan Objectives: The aim of this cohort study was to evaluate whether peripheral natural killer (NK) cell activity was associated with recurrent miscarriage (RM). Methods: With approvals from institutional ethical board, 160 consecutively seen non-pregnant women who had a history of two or more RM were enrolled between June 2009 and December 2014. Peripheral NK cell activity was measured, and compared between RM women with a risk factor/etiology and RM women without the index risk factor/etiology. Furthermore, in RM women who subsequently became pregnant, NK cell activity was compared according to pregnancy outcomes. Results: NK cell activities in RM women who had chromosome abnormality of the couple (p < 0.05), antiphospholipid antibody syndrome (p < 0.01) and positive tests for anti-nuclear antibody (p < 0.01) were lower than those in women without the index risk factor/etiology. In a cohort study of subsequent 105 pregnancies, NK cell activity prior to pregnancy in RM women whose subsequent pregnancies ended in miscarriage with a normal chromosome karyotype of a fetus (n = 17) (median 34.0; range 9–66%) was higher than those in live birth (n = 68) (25.5; 4–59%, p < 0.05) and miscarriage with an abnormal chromosome karyotype of a fetus (n = 9) (24.0; 4–40%, p = 0.055). RM women with >32% of peripheral NK cell activity had a high risk of MN (OR 4.1, 95%CI 1.4–14.3) in the next pregnancy. Conclusion: An increase in peripheral NK cell activity might be involved in pathophysiology underlying RM. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.068
60 Role of matrix metalloproteinase-2 and 9 in pathogenesis of patients with recurrent pregnancy loss Ryosuke Mori 1,∗ , Yasuhiko Ozaki 1 , Shinobu Goto 1 , Fumiko Ozawa 1 , Yuki Obayashi 2 , Yasushi Matsukawa 1 , Tamao Kitaori 1 , Mayumi Sugiura-Ogasawara 1 1
Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan 2 Kasugai Maternity Clinic, Kasugai, Aichi, Japan The findings we reported suggested that the regulatory mechanism of protease and inhibitors such as calpain-calpastatin and cathepsin-cystatin system might play an important role in pathogenesis of recurrent pregnancy loss (RPL). Matrix metalloproteinases (MMPs), which degrade protein of extracellular matrix, are important for forming placenta in early pregnancy. In this study, we investigated a role of MMPs in patients with RPL. With informed consent, decidua, villi and cervical mucous were collected from patients with RPL. A chromosome analysis of villi was performed using G-band staining. We investigate the expression of MMP-2 and MMP-9 using immunohistochemistry and ELISA. Non parametric analysis was applied for statistical comparison of differences. By immunohistochemistry, the staining of MMP-9 was detected in the cytoplasm of stromal and epithelial cells in decidua and villi. In normal chromosome group (n = 7), the expression of MMP2 is significantly lower than abnormal chromosome group (n = 10, p < 0.05) and the expression of MMP-9 is significantly higher than abnormal chromosome group (n = 10, p < 0.05). The results suggested that increased MMP-9 which is controlled by activated neutrophilic leukocyte and reduced MMP-2 which is caused by histological disorder play an important role in pathogenesis of RPL. In additional genetic study, we investigated the association of MMP-2 and MMP-9 gene promoter polymorphisms with patients with RPL. But no statistical significant differences were found in distribution of MMP-2 and MMP-9 genotypes between patients (n = 107) and controls (n = 320). Our findings suggested that MMP2 and MMP-9 gene polymorphisms might not be associated with pathogenesis of RPL. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.069 61 NK1.1+ iNKT cells in the myometrium activated by ␣-galactosylceramide cause fetal loss in mice Tomoko Ichikawa 1,2,∗ , Toshiyuki Negishi 1,2 , Masumi Shimizu 2 , Toshiyuki Takeshita 2 , Hidemi Takahashi 1 1 Department of Microbiology and Immunity, Nippon Medical School, Japan 2 Department of Obstetrics and Gynecology, Nippon Medical School, Japan
DEC-205+ DCs, which are responsible for the innate immunity, induce miscarriages via IL-12 suggest that the activation of invariant NKT (iNKT) cells expressing IL-12 receptors may cause fetal loss. Here, we investigated whether ␣-galactosylceramide (␣-GC), which is a known glycolipid having an ability to activate iNKT cells,
Abstracts / Journal of Reproductive Immunology 118 (2016) 109–141
HIVIg was applied for 69 women with histories of four or more consecutive RM of unexplained etiology. The live birth rate was 89.3% and pregnancy complications such as premature delivery (18%), fetal growth restriction (12%) and cleft lip (in one case) were observed, while severe adverse effects were not observed in women. 60gIVIg was applied for 14 women with history of six or more RM of unexplained etiology between 2010 and 2013. The live birth rate was 30.8%, so significant increase in the live birth rate was not observed with 60gIVIg. The HIVIg may be effective for RM of unexplained etiology, whereas the 60gIVIg was not effective for RM. A randomized double blind placebo control study of HIVIg for RM of unexplained etiology is ongoing in Japan. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.067 59 Natural killer cell activity in women with recurrent miscarriage Yasuhiko Ebina ∗ , Yukari Nishino, Masashi Deguchi, Yoko Maesawa, Yuki Nakajima, Hideto Yamada Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan Objectives: The aim of this cohort study was to evaluate whether peripheral natural killer (NK) cell activity was associated with recurrent miscarriage (RM). Methods: With approvals from institutional ethical board, 160 consecutively seen non-pregnant women who had a history of two or more RM were enrolled between June 2009 and December 2014. Peripheral NK cell activity was measured, and compared between RM women with a risk factor/etiology and RM women without the index risk factor/etiology. Furthermore, in RM women who subsequently became pregnant, NK cell activity was compared according to pregnancy outcomes. Results: NK cell activities in RM women who had chromosome abnormality of the couple (p < 0.05), antiphospholipid antibody syndrome (p < 0.01) and positive tests for anti-nuclear antibody (p < 0.01) were lower than those in women without the index risk factor/etiology. In a cohort study of subsequent 105 pregnancies, NK cell activity prior to pregnancy in RM women whose subsequent pregnancies ended in miscarriage with a normal chromosome karyotype of a fetus (n = 17) (median 34.0; range 9–66%) was higher than those in live birth (n = 68) (25.5; 4–59%, p < 0.05) and miscarriage with an abnormal chromosome karyotype of a fetus (n = 9) (24.0; 4–40%, p = 0.055). RM women with >32% of peripheral NK cell activity had a high risk of MN (OR 4.1, 95%CI 1.4–14.3) in the next pregnancy. Conclusion: An increase in peripheral NK cell activity might be involved in pathophysiology underlying RM. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.068
60 Role of matrix metalloproteinase-2 and 9 in pathogenesis of patients with recurrent pregnancy loss Ryosuke Mori 1,∗ , Yasuhiko Ozaki 1 , Shinobu Goto 1 , Fumiko Ozawa 1 , Yuki Obayashi 2 , Yasushi Matsukawa 1 , Tamao Kitaori 1 , Mayumi Sugiura-Ogasawara 1 1
Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan 2 Kasugai Maternity Clinic, Kasugai, Aichi, Japan The findings we reported suggested that the regulatory mechanism of protease and inhibitors such as calpain-calpastatin and cathepsin-cystatin system might play an important role in pathogenesis of recurrent pregnancy loss (RPL). Matrix metalloproteinases (MMPs), which degrade protein of extracellular matrix, are important for forming placenta in early pregnancy. In this study, we investigated a role of MMPs in patients with RPL. With informed consent, decidua, villi and cervical mucous were collected from patients with RPL. A chromosome analysis of villi was performed using G-band staining. We investigate the expression of MMP-2 and MMP-9 using immunohistochemistry and ELISA. Non parametric analysis was applied for statistical comparison of differences. By immunohistochemistry, the staining of MMP-9 was detected in the cytoplasm of stromal and epithelial cells in decidua and villi. In normal chromosome group (n = 7), the expression of MMP2 is significantly lower than abnormal chromosome group (n = 10, p < 0.05) and the expression of MMP-9 is significantly higher than abnormal chromosome group (n = 10, p < 0.05). The results suggested that increased MMP-9 which is controlled by activated neutrophilic leukocyte and reduced MMP-2 which is caused by histological disorder play an important role in pathogenesis of RPL. In additional genetic study, we investigated the association of MMP-2 and MMP-9 gene promoter polymorphisms with patients with RPL. But no statistical significant differences were found in distribution of MMP-2 and MMP-9 genotypes between patients (n = 107) and controls (n = 320). Our findings suggested that MMP2 and MMP-9 gene polymorphisms might not be associated with pathogenesis of RPL. Conflicts of interest: The authors have no conflict of interest to declare. http://dx.doi.org/10.1016/j.jri.2016.10.069 61 NK1.1+ iNKT cells in the myometrium activated by ␣-galactosylceramide cause fetal loss in mice Tomoko Ichikawa 1,2,∗ , Toshiyuki Negishi 1,2 , Masumi Shimizu 2 , Toshiyuki Takeshita 2 , Hidemi Takahashi 1 1 Department of Microbiology and Immunity, Nippon Medical School, Japan 2 Department of Obstetrics and Gynecology, Nippon Medical School, Japan
DEC-205+ DCs, which are responsible for the innate immunity, induce miscarriages via IL-12 suggest that the activation of invariant NKT (iNKT) cells expressing IL-12 receptors may cause fetal loss. Here, we investigated whether ␣-galactosylceramide (␣-GC), which is a known glycolipid having an ability to activate iNKT cells,