Fetal microchimerisms in the mother: Immunologic implications

Abstract

The previously held concept that the fetus is completely separated from the mother, especially by trophoblasts that line the outer layer of the placenta, has recently been questioned. It has recently been shown that fetal cells are detectable not only in the peripheral blood, but also in maternal skin and liver. Although the migration of fetal cells into the maternal circulation has been given a great deal of attention because of its implication in the prenatal diagnosis of genetic diseases, the potential role of such placental transfer of fetal cells in the pathogenesis of autoimmune diseases has only recently been considered. In patients with scleroderma, fetal cell-derived DNA was detected more frequently in the peripheral blood of patients than controls. This finding of a limited number of fetal cells in maternal tissues leading to microchimerism has been proposed to have a role in the induction of scleroderma. Although evidence for microchimerism has also been confirmed in a high frequency of liver tissues from patients with primary biliary cirrhosis (PBC), a similar high frequency was noted in control patients, which suggests that microchimerism by itself is unlikely to fully account for the pathogenesis of PBC. The finding of such a high frequency of fetal microchimerism in the liver suggests that this is a very common event, raising the possibility that the migration of fetal cells may be important in the induction and subsequent maintenance of tolerance against the fetus during pregnancy. In addition, it is clearly possible that such microchimerism could contribute to the pathogenesis of select autoimmune diseases. Copyright 2000 by the American Association for the Study of Liver DiseasesA lthough the fetus in the uterus is sequestered from the mother by the placenta, this is not a mechanically complete barrier. Several examples show that fetal cells migrating into the maternal body can be found in such tissues as blood and skin. Fetal-derived DNA can be detected in maternal peripheral blood at early stages of gestation and persist long after pregnancy. Recently, our laboratory has also shown that fetal cell-derived genes are detectable in maternal liver tissue, in some cases as long as 43 years after pregnancy. Whether this microchimerism, i.e., migration and presence of fetal cells within maternal tissues, has an important role in either physiological or immunologic function is unclear, but the very high detection rate of fetal-derived DNA in the mother provides suggestive evidence that microchimerism may not be an uninvolved bystander. We review recent studies showing microchimerism in the mother and address its putative role in autoimmunity and the maintenance of tolerance against the fetus.

Male cell microchimerism in normal and diseased female livers from fetal life to adulthood

“…In the literature, male liver microchimerism was mainly explored in the setting of primary biliary cirrhosis, and in most studies, the frequency of male liver microchimerism was similar in women with primary biliary cirrhosis and in controls. 2,30 In this study, we tested acute and chronic liver diseases and failed to disclose any relationship between the presence and degree of male microchimerism and the existence and intensity of liver disease.…”

Neonatal Lymphocytes Dominate against Lymphocytes of Their Own Mother but Not against Allogenic Maternal or Adult Lymphocytes in Bidirectional Mixed Lymphocyte Cultures

“…On the other hand, the tolerance of the fetal cells by the mother leads to fetalmaternal microchimerisms, which can be demonstrated many years after pregnancy. Although evidence of microchimerism has also been confirmed with a high incidence in liver tissues from patients with primary biliary cirrhosis, a high frequency has also been noted in control patients, suggesting that microchimerism alone is unlikely to fully account for the pathogenesis of this disease [34]. It is still unclear whether the development of the maternofetal as well as the feto-maternal microchimerism finds its etiology in disturbances of the feto-maternal immune balance.…”

Superior survival of blood and marrow stem cell recipients given maternal grafts over recipients given paternal grafts

“…6 On the other hand, about half of the patients receiving multiple transfusions as adults did not form antibodies against the non-inherited maternal HLA antigens, 7 indicating the persistence of acquired B cell unresponsiveness to maternal antigens into adult life. More surprisingly, semi-allogeneic fetal hematopoietic cells were detectable from parous women not only during gestation but also many years after childbirth, [8][9][10][11] suggesting a long-lasting form of the maternal tolerance to fetal HLA antigens of paternal origin.To date, the role of such previous experience of maternal-fetal tolerance in allogeneic hematopoietic stem cell transplantation is unknown. However, several reports on solid allograft transplants have suggested the persistence of a favorable 'maternal-fetal effect' even after the cessation of pregnancy.…”

“…6 On the other hand, about half of the patients receiving multiple transfusions as adults did not form antibodies against the non-inherited maternal HLA antigens, 7 indicating the persistence of acquired B cell unresponsiveness to maternal antigens into adult life. More surprisingly, semi-allogeneic fetal hematopoietic cells were detectable from parous women not only during gestation but also many years after childbirth, [8][9][10][11] suggesting a long-lasting form of the maternal tolerance to fetal HLA antigens of paternal origin.…”