Association of Anti-Phospholipid Antibody in Patients'sera with Habitual Abortion and Abnormal Pregnancies

习惯性流产及异常妊娠患者血清抗磷脂抗体的相关性

• 批准号: 01480397
• 负责人: YAGAMI Yoshiaki
• 金额: $ 3.78万
• 依托单位: Nagoya City University Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480397/
• 关键词: HABITUAL ABORTION; ANTI-PHOSPHOLIPID ANTIBODY; ELISA; ANTI-GM3 ANTIBODY; PREDNISOLONE-ASPIRIN THERAPY; PRE-ECLAMPSY; PROSTACYCLIN; INTRAUTERINE GROWTH RETARDATION; ステロイド・アスピリン治療; 流産; ハイドロキシルアパタイト; 血管内皮細胞; プロスタサイクリン; 胎盤; アフィニティ精製抗体; ニトロセルロ-ス

1. We established an ELISA system to detect antibodies (lgG, lgM) against 6 phospholipid antigens (PA, PS, Pl, PG, CL and PE) in patient sera. Twelve kinds of anti-phospholipid antibodies were measured in the sera of 216 healthy non-pregnant women, and the respective normal upper limits were determined (mean+3SD). The possible relationships were then investigated between the anti-phospholipid antibodies and various abnormal pregnancies (e.g., habitual abortion, pre-eclampsy, intrauterine growth retardation;IUGR). Some 14.6% in the sera of 328 habitual aborters proved to be antiphospholipid antibody positive, and 83% of them aborted in their next pregnancy. However, when they were treated with a combination prednisolone (antibody suppressant)- aspirin (antithrombosis agent), all cases showed a decease in antibody level and 71.5% of them gave birth. This suggests that high levels of anti-phospholipid antibodies have adverse effects on maintenance of pregnancy. Particularly, lgG anti-phos … More pholipid antibody was detected frequently on the cases of pre-eclampsy, IUGR and neonatal respiratory insufficiency. It was thus obvious that lgG anti-phospholipid antibodies had deleterious effects on feto-placental circulation.2. We also measured antibodies (lgG, lgM) against glycolipid antigen (GM3) in patient sera using this ELISA system. About half the patients who showed high levels of both antibodies against phospholipid and glycolipid (GM3) did not respond to prednisolone-aspirin therapy and the following pregnancy resulted in abortion. Anti-GM3 antibody is suggested to enhance the reactivity of antiphospholipid antibody with the cell membrance.3. An lgG class specific antibody was purified from the anti-phospholipid antibody positive sera using affinity column chromatography. This affinity purified anti-phospholipid antibody (APA) was reacted with cultured endotherial cells of the humanumbilical cord artery, and the effect of the APA on prostacyclin (PG12) production was examined. The APA by itself was not effective, but in the presence of beta2-glycoprotein I, the APA inhibited the PG12 production from the endotherial cell. On the other hand, the APA reacted with cell surface membrane fractions separated from the normal placental villi. These observations indicate that anti-phospholipid antibody exerts an influence upon the cell surface membrane. Less

1.建立了检测患者血清中6种磷脂抗原(PA、PS、Pl、PG、CL和PE)的抗体(LgG、LGM)的酶联免疫吸附试验体系。对216例健康非妊娠妇女血清中12种抗磷脂抗体进行了检测，并确定了相应的正常上限(平均值+3SD)。然后研究了抗磷脂抗体与各种异常妊娠(如习惯性流产、先兆子痫、胎儿宫内发育迟缓；IUGR)之间的可能关系。328例习惯性流产者血清抗磷脂抗体阳性率为14.6%，其中83%在下次妊娠时流产。但经强的松龙(抗体抑制药)-阿司匹林(抗血栓药)联合治疗后，所有患者的抗体水平均下降，71.5%的患者分娩。这表明，高水平的抗磷脂抗体对维持妊娠有不利影响。特别是LGG反PHOS…子痫前期、胎儿宫内发育迟缓、新生儿呼吸功能不全者磷脂抗体阳性率高。由此可见，LGG抗磷脂抗体对胎盘循环有不良影响。我们还用该系统检测了患者血清中抗糖脂抗原(GM3)的抗体(LGG、LGM)。在抗磷脂和糖脂(GM3)抗体水平都很高的患者中，约有一半的患者对强的松龙-阿司匹林治疗没有反应，并在下一次怀孕后导致流产。提示抗GM3抗体可增强抗磷脂抗体与细胞膜的反应性。用亲和柱层析法从抗磷脂抗体阳性血清中纯化出一种特异性抗体。亲和纯化的抗磷脂抗体(APA)与培养的人脐动脉内皮细胞反应，检测APA对前列环素(PG12)产生的影响。APA本身不起作用，但在β2-糖蛋白I存在的情况下，APA抑制内皮细胞产生PG12。另一方面，APA与从正常胎盘绒毛中分离出来的细胞表膜部分发生反应。这些观察结果表明，抗磷脂抗体对细胞表面膜产生影响。较少

项目成果

Sasaki,M.,Kunimatsu,M.,Tada,T.,Nishimura,J.,MA,X.J.,and Ohkubo,I.: "Calpain and kininogen mediated inflammation," Biomed.Biochim.Acta. 50. 499-508 (1991)

Sasaki, M.、Kunimatsu, M.、Tada, T.、Nishimura, J.、MA, X.J. 和 Ohkubo, I.：“钙蛋白酶和激肽原介导的炎症”，Biomed.Biochim.Acta。

林 弥生、青木 耕治、八神 喜昭、鈴木 重澄、側島 久典、戸苅 創、和田 義郎、その他: "原因不明の呼吸障害をきたした抗リン脂質lgG抗体陽性新生児の1症例" 日本新生児学会雑誌. 28. 114-119 (1992)

Yayoi Hayashi、Koji Aoki、Yoshiaki Yagami、Shigezumi Suzuki、Hisanori Sojima、Hajime Tokari、Yoshiro Wada 等：“抗磷脂 IgG 抗体阳性新生儿不明原因呼吸系统疾病的病例”日本新生儿学会杂志 28. 114。 -119 (1992)

Sasaki, M., Kunimatsu, M. and Ohkubo, I.: "Role of calpains and kininogens in inflammation" Acta Biologica Hangarica. 42(1-3). 231-242 (1991)

Sasaki, M.、Kunimatsu, M. 和 Ohkubo, I.：“钙蛋白酶和激肽原在炎症中的作用”Acta Biologica Hangarica。

八神 喜昭、青木 耕治: "異常妊娠の原因としての抗リン脂質抗体" 病態生理. 9. 657-659 (1990)

Yoshiaki Yagami、Koji Aoki：“抗磷脂抗体是异常妊娠的原因”病理生理学 9. 657-659 (1990)。

Aoki, K., Hayashi, Y. and Yagami, Y.: "Anti-phospholipid antibody and pregnancy" Syusankigaku symposium. 9. 29-36 (1991)

Aoki, K.、Hayashi, Y. 和 Yagami, Y.：“抗磷脂抗体与妊娠”Syusankigaku 研讨会。