|Budget Amount *help
¥5,900,000 (Direct Cost : ¥5,900,000)
Fiscal Year 1991 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1990 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1989 : ¥4,200,000 (Direct Cost : ¥4,200,000)
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
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