Maternal-fetal microchimerism and fetal-juvenile malignancies

Abstract

Maternal-fetal microchimerism has been discovered, when male (XY) cells were identified in the circulation and organs of mothers, who had sons and in the cord blood, circulation and organs of the newborns and sons. The quantitative estimation of the microchimeric cells could be assessed during the last decade, when the sensitive real time PCR technology became available. The maternal cells are accepted by the fetal organism easily. The transferred fetal cells are pluripotent stem cells, not expressing HLA class I antigens, but expressing tolerogenic HLA-G membrane antigens. The stem cells were shown to be able to differentiate, and repair the maternal tissues if impaired or diseased. Antibody producing B lymphocytes are also participating in the bidirectional microchimerism, proven by the appearance of IgM, IgG, IgA and IgE antibodies in the maternal circulation of pregnants suffering from agammaglobulinemia, and or IgA, IgE or IgM deficiencies. The maternal fetal microchimerism is probably responsible for the transfer of virus-carrier cells or latently virus-infected cells into the fetus. The transfer of tumour cells is bidirectional. The influence of pregnancy to the maternal oncology is very complicated, therefore it is discussed in a separate chapter. The incidence of transmission of maternal malignancies was found to be 1/1,000 pregnancies. The explanation for this is the hematopoietic and antitumour effect of the placenta and of the fetal mesenchymal cells (Tokita et al. 2001). The fetal tumours can be of maternal origin. Premalignant cells can be also transferred into the fetal organs, these cells require according to certain professionals a second (or third) hit to begin malignant multiplication. The premalignant microchimeric cells will suffer the last hit for malignant transformation in childhood or later. The epidemiological data support this assumption. Childhood tumours, however, may be of primordial cell origin, too. The transplacental maternal-fetal transmission of cells carrying oncogenic viruses are suggested to induce post partum malignancies due to the immunotolerance against virus-coded proteins during pregnancy (Burkitt-lymphoma, Kaposi's sarcoma, nasopharingeal carcinoma, carcinoma of head and neck, certain liver and genital cancers). Maternal-fetal microchimerism induce lifelong immunological consequences. The incidence of successful organ and stem cell transplantation was higher when the donor recipient partners are mother and their children. The graft versus host and host versus graft diseases are also more successful in the same combination, than any other combinations except the monozygotic twins. The breast feeding was shown to be advantageous for the mother-child donor recipient partners. There are observations, suggesting the role of microchimerism in the development of autoimmune diseases and long term transgenerational transmission of genes, viruses and genetic information even from the grandparents to the children and grandchildren. The newborns may carry maternal cells 20-30 years older than their own age and even 40-50 years old cells of grandmother origin (Fig. 10.1). Fig. 10.1 Maternal-fetal transgenerational microchimerism. Bidirectional transfer of cells occurs in the 2nd and 3rd trimester of the pregnancy. The fetal cells were shown to persist in the maternal organism for decades. A certain percentage of the pregnants carries microchimeric cells of the grandmother (horizontal black triangles). These cells of the grandmother are 20-30 years older than the mothers age. Even the younger siblings might obtain stem cells from the grandmother and from the mother (open horizontal triangles of siblings 1 and 2). These microchimeric cells of grandmother origin transfered from the mother to fetuses are 40-60 years older than the siblings themselfs. The microchimaric cells of maternal origin are also 20-30 years older than the cells of the siblings themselves. On the other hand, the siblings supplied fetal cells 20-30 years younger than the mother's age. The children's malignancies are diagnosed at a decreasing incidence upto the fifth years of age (grey horizontal triangle drawn with broken line). The incidence of maternal malignancies accumulate between 20 and 40 years of age. Unfortunately the origin of the malignancies had not been tested up to now at least for half of either maternal or the children's malignancies The chapter is completed with data on horizontal transmission of malignant tumours in the animal world probably due to the inbred character of the populations (Cooper et al. 1964; O'Brien et al. 1985).