Establishment of a recurrent spontaneous abortion mouse model by intrauterine immunization and development of a new treatment

宫内免疫建立复发性流产小鼠模型及新疗法的开发

• 批准号: 08671855
• 负责人: YAMADA Hideto
• 金额: $ 1.47万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671855/
• 关键词: Recurrent spontaneous abortion; Immunoglobulin; Antiphospholipid synbrom; 生殖免疫学

The aim of this study is to investigate the efficacy of massive intravenous immunoglobulin (MIVIg) treatment for women with a history of recurrent spontaneous abortion (RSA) due to unexplained etiology. Subjects consisted of 9 women and 11 pregnancies having history of 4 or more consecutive RSA with unexplained etiology and no live births. Mean number of fetal losses is 4.5 (ranged from 4 to 6 abortions). Over the course of 5 days, at 20 g/day, immunoglobulin has been infused intravenously duning 4-7 gestational week (GW). No additional infusion has been performed. Two pregnancies resulted in missed abortions at 6 and 7GW,respectively. Mosaicism (46XX/48XX,+16, +20), and tetraploidy (92XXXX) were found by chromosome analyzes of the two abortus. Eight out of the other 9 pregnancies resulted in full term deliveries of healthy neonates. One pregnancy developed an intrauterine growth retardation and fetal distress, resulting in a premature delivery (30GW) by cesarean section. Thus, excluding the 2 abortions with chromosome aberrations, the MIVIg treatment was effective in all 9 pregnancies of RSA women with unexplained etiology. This MIVIg treatment (100g administered in early gestation) may be a benefical alternative to previous IVIg infusion methods and should be evaluated in further studies employing a larger number of homogeneous patients who fall into a high risk catagory of first trimester abortions.

本研究的目的是探讨大量静脉注射免疫球蛋白（MIVIg）治疗的妇女的历史反复自然流产（RSA），由于不明原因的病因。受试者包括9名女性和11名妊娠，有4次或以上连续RSA病史，病因不明，无活产。平均胎儿丢失数为4.5（范围为4 - 6次流产）。在5天的过程中，以20 g/天，在4-7孕周（GW）静脉内输注免疫球蛋白。未进行额外输注。两次妊娠分别在6和7 GW时导致漏诊流产。染色体分析发现两个流产儿的核型为嵌合体（46 XX/48 XX，+16，+20）和四倍体（92 XX）。另外9例妊娠中有8例足月分娩健康新生儿。1例妊娠发生宫内发育迟缓和胎儿窘迫，导致剖宫产早产（30 GW）。因此，排除2例染色体畸变流产，MIVIg治疗在所有9例病因不明的RSA女性妊娠中均有效。这种MIVIg治疗（在妊娠早期给予100 g）可能是以前IVIg输注方法的有益替代方法，应在采用大量同质患者的进一步研究中进行评估，这些患者属于妊娠早期流产的高风险类别。

项目成果

Yamada, H: "Hematopoietic cytokine levels and in vitro colony formation assay in fetal anemia." Seminar in Thrombosis and Hemostasis. accepted(印刷中). (1998)

Yamada, H：“胎儿贫血中的造血细胞因子水平和体外集落形成测定。”血栓形成和止血研讨会已接受（1998 年出版）。

Yamada, H: "Massive immunoglobulin treatment in women with primary,four or more recurrent spoutaneous abortions due to unexplained etiology." Hum Reprod. accepted(印刷中). (1998)

Yamada, H：“对因原因不明的原发性、四次或以上复发性流产的妇女进行大量免疫球蛋白治疗。”Hum Reprod（1998 年出版）。

Yamada H: "Massive immunoglobulin treatment in women with primary,four or more recurrent spontaneous abortions due to unexplained etiology." Hum Reprod (accepted). (印刷中). (1998)

Yamada H：“对因原因不明的原发性、四次或以上复发性流产的妇女进行大量免疫球蛋白治疗。”Hum Reprod（已接受）（1998 年）。

山田 秀人: "習慣流産をとめる-疫学と状況." 臨床婦人科産科. 50(5). 628-632 (1996)

Hideto Yamada：“阻止习惯性流产 - 流行病学和情况。” 50(5) (1996)。

Sasaki T: "Increased frequency of HLA-DR4 allele in women with unexplained recurrent spontaneous abortions,detected by the method of PCR-SSP." Journal of Reproductive Immunology. 22. 273-279 (1997)

Sasaki T：“通过 PCR-SSP 方法检测到不明原因反复自然流产的女性 HLA-DR4 等位基因频率增加。”