Advances with molecular biological techniques have resulted in the recent recognition of bilateral traffic of cells at the maternal-fetal interface. Fetal cells can be detected in 90 percent of women in the first trimester of pregnancy. Appreciation of the frequency with which maternal cells are present in cord blood has also increased from earlier estimates of only 1 percent to more than 40 percent of cord blood samples. Unexpectedly, Bianchi et al recently found that CD34+CD38+ (progenitor) fetal cells can also persist in the maternal circulation for up to 27 years after pregnancy. Progenitor cells are capable of differentiation into the lymphoid lineage. Persistent maternal cells have been found in the circulation of infants with severe combined immunodeficiency. However, studies have not examined whether maternal cells persist at low levels in apparently normal offspring. Lending support to the possibility, cytogenetic studies of male infants in whom the mother was the donor for in utero transfusion revealed that 2-4 percent of lymphocytes were XX at 4 to 5 years of age. Since the fetal immune system is in the process of developing, and in light of the findings of Bianchi etal, persistence of maternal cells not be surprising. HLA molecules are the primary determinants of what is self and what is foreign . In human populations there is a great deal of diversity in HLA molecules. However, the diversity is finite so that sometimes a mother and child will be HLA identical, and sometimes, if one of the two is HLA homozygous, they will be HLA-compatible from the perspective of on individual and incompatible from the perspective of the other. The question thus arises as to how the HLA-relationship of mother and child might affect subsequent chimerism. A final question addresses the biological significance of chimerism resulting from pregnancy. Human conditions of chimerism, such as graft-versus-host disease after bone marrow transplantation, are characterized by anti-nuclear antibodies, and have clinical features in common with some human autoimmune disease such as scleroderma, Sjogren's syndrome, myositis, primary biliary cirrhosis and systemic lupus erythematosus (SLE). Studies in animal models indicate that chimerism can produce autoimmune disease. Introduction of parent cells into F1 is a recognized model for SLE. The purpose of the proposed studies is to define the role of the maternal- fetal HLA relationship in chimerism resulting from pregnancy and to examine the potential significance of this with respect to the autoimmune disease, SLE.
| Nelson, J L (1999) Non-host cells in the pathogenesis of autoimmune disease: a new paradigm? Ann Rheum Dis 58:518-20 |
| Nelson, J L (1999) Microchimerism: implications for autoimmune disease. Lupus 8:370-4 |
