Maternal immune responses to the fetus in early pregnancy and recurrent miscarriage

Direct evidence that maternal immune rejection of the fetus causes some unexplained recurrent spontaneous abortions was sought in 18 women with this condition. Tests of maternal cell-mediated immunity to fetal (paternal) antigens were done before conception, in early pregnancy, and at miscarriage, and were compared with those in 10 controls in their first pregnancies. Maternal cytotoxic alloantibody production and the blocking effect of maternal sera on maternal lymphocyte activation were also evaluated. There was no evidence for maternal cell-mediated reactivity to paternal antigens in normal early pregnancy or in most women who aborted, but circulating cytotoxic cells were found at miscarriage in a third of affected women. There was no correlation between the production of cytotoxic antibodies and serum blocking activity, and the success of the pregnancy. These data provide evidence that cell-mediated immune reactivity may be changed in some women who abort recurrently but show that circulating immunological blocking factors are not relevant to the success of pregnancy. Their induction by maternal immunisation with paternal leucocytes does not explain why this procedure prevents recurrent spontaneous abortions.