Chimerism and tetragametic chimerism in humans: implications in autoimmunity, allorecognition and tolerance

Abstract

The presence of cells or tissues from two individuals, chimeras, or the presence of cells and tissues that include the gonads, tetragametic chimerism can be detected by the analysis of cytogenetics and analysis of polymorphic genetic markers, using patterns of pedigree inheritance. These methodologies include determination of sex chromosomes, major histocompatibility complex (MHC) polymorphisms and panels of short tandem repeats (STRs) that include mitochondrial DNA markers. Studies routinely involve cases of temporal chimerism in blood transfusion, or following allotransplantation to measure the outcome of the organ, lymphopoietic tissues or bone marrow grafts. Demonstration of persistent chimerism is usually discovered in cases of inter-sexuality due to fusion of fraternal twins or in cases of fusion of embryos with demonstrable allogeneic monoclonality of blood which, excluded maternity or paternity when blood alone is used as the source of DNA. In single pregnancies it is possible to produce two kinds of microchimerism: feto-maternal and materno-fetal, but in cases of fraternal twin pregnancies it is possible to identify three different kinds which are related to cases of vanishing twins that can be identified during pregnancy by imaging procedures; (1) hematopoietic, (2) gonadal, and (3) freemartins when the twins have different sex and the individual born is a female with either gonadal or both gonadal and hematopoietic tissues. Fraternal twin pregnancies can also produce fusion of embryos. Such cases could be of different sex presenting with inter-sexuality or in same sex twins. One of such cases, the best studied, showed evidence of chimerism and tetragametism. In this regard, the case was studied because of disputed maternity of two of her three children. All tissues studied, except for the blood, demonstrated four genetic components but only two in her blood of four possible showed allogeneic monoclonality consistent with the interpretation that her blood originated from one hematopoietic stem cell. Also, microchimerism, due to traffic of cells via materno-fetal or feto-maternal has been prompted by reports of their potential association with the development of autoimmune disorders including systemic lupus erythematosus (SLE) and systemic sclerosis, and in allotransplantation. In addition, their relevance of chimerism in the positive and negative selection of T cells in the thymus has not been addressed. T lymphocytes play a central role in controlling the acquired immune response and furthermore serve as crucial effector cells through antigen specific cytotoxic activity and the production of soluble mediators. Central tolerance is established by the repertoire selection of immature T lymphocytes in the thymus, avoiding the generation of autoreactive T cells. Expression of chimeric antigens in the thymus could modify the generation of specific T cell clones in chimeric subjects and these mechanisms could be important in the induction of central tolerance against foreign antigens important in allo-transp...

Preanalytical Variables Affecting the Integrity of Human Biospecimens in Biobanking

“…A disadvantage is the low concentration of analytes (67 ). The advantage of extracting DNA from saliva is that the germline DNA represents only the DNA from the person who donated, compared to DNA derived from blood which could originate from other persons, such as in cases of multiple transfusions or chimerism after bone marrow transplantation (68,69 ). Furthermore, salivary DNA is a useful source of germline DNA in studies of hematologic neoplasias (70 ).…”

A molecular basis for developmental plasticity in early mammalian embryos

“…In particular, the use of in vitro fertilisation for assisted conception, in which more than one embryo is transferred, has resulted in an increase in the number of chimaeras arising from the aggregation of embryos (Quintero et al, 2003;Souter et al, 2003). In many cases, chimaerism results from the transportation of cells between individuals via the shared circulating blood and involves organs with a good blood supply (van Dijk et al, 1996); in some instances, it extends to the germ cells (van Dijk et al, 1996;Yunis et al, 2007).…”

“…In particular, the use of in vitro fertilisation for assisted conception, in which more than one embryo is transferred, has resulted in an increase in the number of chimaeras arising from the aggregation of embryos (Quintero et al, 2003;Souter et al, 2003). In many cases, chimaerism results from the transportation of cells between individuals via the shared circulating blood and involves organs with a good blood supply (van Dijk et al, 1996); in some instances, it extends to the germ cells (van Dijk et al, 1996;Yunis et al, 2007).Murine chimaeras have been generated by the aggregation of embryos (Tarkowski, 1961;Mintz, 1962; Gardner, 1968; Gardner and Munro, 1974). This technique, when performed with embryos of different genotypes, has become a useful experimental device for generating mosaics and allows studies of gene function by creating organisms with cells of different genotypes (Fig.…”

Immune reactivity to type VII collagen: implications for gene therapy of recessive dystrophic epidermolysis bullosa

“…Immune response to collagen VII V Pendaries et al Immune response to collagen VII V Pendaries et al mother to the fetus across the placenta, 32 and chimerism between dizygotic twins has been shown. 33 Recent experiments have shown that the mammalian fetus can develop antibody responses to antigenic stimuli.…”