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Three cases of unexplained recurrent pregnancy loss with different results for chromosome analysis of chorionic villi
Abstracts / Journal of Reproductive Immunology 112 (2015) 121–140
22 Cancer related fibroblasts (CAFs) control killer activity of natural killer cell through the poliovirus receptor (PVR: CD155) and have an important role for tumor expansion Tomoko Inoue ∗ , Kei Kawana, Katsuyuki Adachi, Ayumi Taguchi, Ken Nagamatsu, Masakazu Sato, Mitsuyo Yoshida, Juri Takahashi, Asaha Fujimoto, Hiroe Kamoto, Aki Yamashita, Kazunori Nagasaka, Yutaka Osuga, Tomoyuki Fujii Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan E-mail address: [email protected] (T. Inoue). Objective: CAF have the important role for cancer progression. Natural killer cell (NK cell) is the main killer cell in microenvironment. Downregulation of Poliovirus receptor (PVR) that is cell surface molecule, reduced killer activity of NK cell and affected cell growth. Our objective is to investigate the difference of normal fibroblast and CAF for natural killer cells in sex organs. Method: We gathered CAF and normal endometrium fibroblast (NEF) from endometrial cancer and compared the killer activity of NK cells when we co-cultured them with NK cell. To confirm which is more important to control the killer activity, the action by humoral factors or their direct contact between CAF and NK cell, CAF and NK cell under the trans-well chamber insertion were cultured. Result: By cocultivation of CAF and NK cell, killer activity of NK cell decreased to 30% in comparison with cocultivation of NEF. NK killer activity was not canceled even if IDO repressor was added. NK killer activity restraint by CAF was totally canceled by the transwell chamber. PVR was focused on because the difference of PVR expression between CAF and NEF. When PVR was knocked down by siRNA, killer activity of NK cell was also reduced. Conclusion: CAF controlled NK killer activity and did not rise in microenvironment. PVR in fibroblast may participate in control of NK activity in not only tumor immunity but also reproduction immunity. http://dx.doi.org/10.1016/j.jri.2015.09.027 23 Three cases of unexplained recurrent pregnancy loss with different results for chromosome analysis of chorionic villi Toshiaki Endo 1,∗ , Tsuyoshi Baba 1 , Yoshika Kuno 1 , Miyuki Morishita 1 , Masahito Mizuuchi 1 , Shinichi Ishioka 1 , Tamotsu Kiya 1,2 , Tsuyoshi Saito 1 1 Department of Obstetrics and Gynecology, School of Medicine, Sapporo Medical University, Japan 2 Ena Ladies’ Clinic, Japan
Based on our experience there appear to be at least 3 types of recurrent pregnancy loss because we had 3 cases with different types of chromosomal findings for the chorionic villi. Our cases: Our case 1 visited our clinic when she was 30 years old. She had experienced 5 miscarriages with no clear causes. Following this, 2 miscarriages occurred even after she was given both low dose aspirin and heparin. Chromosome analysis of the chorionic villi showed a normal karyotype. Case 2 had no clear cause for her 7 recurrent miscarriages. Surprisingly, however,
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she had different types of trisomy of the chorionic villi during 4 miscarriages. Chromosome analysis of her chorionic villi showed 47, XX, +5 at 36 years of age, 47, XX, +7 at 37 years, 47, XX, +16 at 39 years, and 47, XY, +13 when she was 42. She reported that she had taken low dose aspirin. Case 3, who had two unexplained miscarriages, visited our clinic when she was 37 years old. Although we gave her low dose aspirin and heparin, she experienced two more miscarriages, and chromosome analysis of the chorionic villi showed a normal karyotype and 47, XX, +4, respectively. Discussion: We speculate that case 1 possibly had some unknown immunological abnormality and case 2 was a patient who should receive preimplantation genetic diagnosis, However, case 3 may have had a different cause for miscarriage than the other 2 cases. As we have no effective treatment for unexplained recurrent pregnancy loss at present, we hope an ideal treatment will be established in the near future. http://dx.doi.org/10.1016/j.jri.2015.09.028 24 Markers of thrombotic events in autoimmune diseases: Comparison of Antiphospholipid Score (aPL-S) and Global Anti-phospholipid Syndrome Score (GAPSS) Kenji Oku ∗ , Olga Amengual, Hiroyuki Nakamura, Ryo Hisada, Kazumasa Oomura, Masaru Kato, Toshiyuki Bohgaki, Tetsuya Horita, Shinsuke Yasuda, Tatsuya Atsumi Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Japan Objective: Recently, new clinical scoring systems to quantify the probability for the diagnosis of antiphospholipid syndrome (APS) have been proposed in sequence: the Antiphospholipid Score (aPLS) and the Global Antiphoshpholipid Syndrome Score (GAPSS). They are derived from the combinations of independent risks for thrombosis particularly focused on antiphospholipid antibodies profiles (aPL-S) or centered on the existence of each antiphospholipid antibodies taking into account with conventional cardiovascular disease risk (GAPSS). These scores, as well as tools for diagnosis, function as index for predicting future thrombosis in autoimmune diseases. Patients and methods: This study comprised 257 patients with autoimmune diseases who visited Hokkaido University Hospital Rheumatology Clinic between 2002 and 2003 with the follow-up period of more than 5 years (median follow-up periods: 126 (IQR 92.5,133) months). Demographic, clinical data and cardiovascular risk factors were obtained from the medical charts. Lupus Anticoagulant (LAC) assays (3 mixing tests and 2 confirmatory tests), IgG/M anticardiolipin antibodies, IgG/M anti-2-glycoprotein I antibodies and IgG/M phosphatidylserine dependent antiprothrombin antibodies were performed in all subjects. The disease profile of these patients was as follows; 42 APS (17 primary APS), 84 SLE (without APS), 45(18%) rheumatoid arthritis and 85 patients with other autoimmune diseases. To evaluate the diagnostic powers for GAPSS and aPL-S, area under the curve (AUC) of receiver operating characteristic (ROC) curves were calculated. To evaluate the powers of the two scores for thrombosis prediction, Cox proportional hazard regression analyses were performed separately for each score with the cut off derived from the ROC curve. Each risk factor for the multivariate Cox analyses were assessed through separate univariate Cox regression
22 Cancer related fibroblasts (CAFs) control killer activity of natural killer cell through the poliovirus receptor (PVR: CD155) and have an important role for tumor expansion Tomoko Inoue ∗ , Kei Kawana, Katsuyuki Adachi, Ayumi Taguchi, Ken Nagamatsu, Masakazu Sato, Mitsuyo Yoshida, Juri Takahashi, Asaha Fujimoto, Hiroe Kamoto, Aki Yamashita, Kazunori Nagasaka, Yutaka Osuga, Tomoyuki Fujii Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan E-mail address: [email protected] (T. Inoue). Objective: CAF have the important role for cancer progression. Natural killer cell (NK cell) is the main killer cell in microenvironment. Downregulation of Poliovirus receptor (PVR) that is cell surface molecule, reduced killer activity of NK cell and affected cell growth. Our objective is to investigate the difference of normal fibroblast and CAF for natural killer cells in sex organs. Method: We gathered CAF and normal endometrium fibroblast (NEF) from endometrial cancer and compared the killer activity of NK cells when we co-cultured them with NK cell. To confirm which is more important to control the killer activity, the action by humoral factors or their direct contact between CAF and NK cell, CAF and NK cell under the trans-well chamber insertion were cultured. Result: By cocultivation of CAF and NK cell, killer activity of NK cell decreased to 30% in comparison with cocultivation of NEF. NK killer activity was not canceled even if IDO repressor was added. NK killer activity restraint by CAF was totally canceled by the transwell chamber. PVR was focused on because the difference of PVR expression between CAF and NEF. When PVR was knocked down by siRNA, killer activity of NK cell was also reduced. Conclusion: CAF controlled NK killer activity and did not rise in microenvironment. PVR in fibroblast may participate in control of NK activity in not only tumor immunity but also reproduction immunity. http://dx.doi.org/10.1016/j.jri.2015.09.027 23 Three cases of unexplained recurrent pregnancy loss with different results for chromosome analysis of chorionic villi Toshiaki Endo 1,∗ , Tsuyoshi Baba 1 , Yoshika Kuno 1 , Miyuki Morishita 1 , Masahito Mizuuchi 1 , Shinichi Ishioka 1 , Tamotsu Kiya 1,2 , Tsuyoshi Saito 1 1 Department of Obstetrics and Gynecology, School of Medicine, Sapporo Medical University, Japan 2 Ena Ladies’ Clinic, Japan
Based on our experience there appear to be at least 3 types of recurrent pregnancy loss because we had 3 cases with different types of chromosomal findings for the chorionic villi. Our cases: Our case 1 visited our clinic when she was 30 years old. She had experienced 5 miscarriages with no clear causes. Following this, 2 miscarriages occurred even after she was given both low dose aspirin and heparin. Chromosome analysis of the chorionic villi showed a normal karyotype. Case 2 had no clear cause for her 7 recurrent miscarriages. Surprisingly, however,
129
she had different types of trisomy of the chorionic villi during 4 miscarriages. Chromosome analysis of her chorionic villi showed 47, XX, +5 at 36 years of age, 47, XX, +7 at 37 years, 47, XX, +16 at 39 years, and 47, XY, +13 when she was 42. She reported that she had taken low dose aspirin. Case 3, who had two unexplained miscarriages, visited our clinic when she was 37 years old. Although we gave her low dose aspirin and heparin, she experienced two more miscarriages, and chromosome analysis of the chorionic villi showed a normal karyotype and 47, XX, +4, respectively. Discussion: We speculate that case 1 possibly had some unknown immunological abnormality and case 2 was a patient who should receive preimplantation genetic diagnosis, However, case 3 may have had a different cause for miscarriage than the other 2 cases. As we have no effective treatment for unexplained recurrent pregnancy loss at present, we hope an ideal treatment will be established in the near future. http://dx.doi.org/10.1016/j.jri.2015.09.028 24 Markers of thrombotic events in autoimmune diseases: Comparison of Antiphospholipid Score (aPL-S) and Global Anti-phospholipid Syndrome Score (GAPSS) Kenji Oku ∗ , Olga Amengual, Hiroyuki Nakamura, Ryo Hisada, Kazumasa Oomura, Masaru Kato, Toshiyuki Bohgaki, Tetsuya Horita, Shinsuke Yasuda, Tatsuya Atsumi Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Japan Objective: Recently, new clinical scoring systems to quantify the probability for the diagnosis of antiphospholipid syndrome (APS) have been proposed in sequence: the Antiphospholipid Score (aPLS) and the Global Antiphoshpholipid Syndrome Score (GAPSS). They are derived from the combinations of independent risks for thrombosis particularly focused on antiphospholipid antibodies profiles (aPL-S) or centered on the existence of each antiphospholipid antibodies taking into account with conventional cardiovascular disease risk (GAPSS). These scores, as well as tools for diagnosis, function as index for predicting future thrombosis in autoimmune diseases. Patients and methods: This study comprised 257 patients with autoimmune diseases who visited Hokkaido University Hospital Rheumatology Clinic between 2002 and 2003 with the follow-up period of more than 5 years (median follow-up periods: 126 (IQR 92.5,133) months). Demographic, clinical data and cardiovascular risk factors were obtained from the medical charts. Lupus Anticoagulant (LAC) assays (3 mixing tests and 2 confirmatory tests), IgG/M anticardiolipin antibodies, IgG/M anti-2-glycoprotein I antibodies and IgG/M phosphatidylserine dependent antiprothrombin antibodies were performed in all subjects. The disease profile of these patients was as follows; 42 APS (17 primary APS), 84 SLE (without APS), 45(18%) rheumatoid arthritis and 85 patients with other autoimmune diseases. To evaluate the diagnostic powers for GAPSS and aPL-S, area under the curve (AUC) of receiver operating characteristic (ROC) curves were calculated. To evaluate the powers of the two scores for thrombosis prediction, Cox proportional hazard regression analyses were performed separately for each score with the cut off derived from the ROC curve. Each risk factor for the multivariate Cox analyses were assessed through separate univariate Cox regression