ScienceWeek

MEDICAL BIOLOGY: ON MICROCHIMERISM

The following points are made by K.M. Adams and J.L Nelson (J. Am. Med. Assoc. 2004 291:1127):

1) The term "microchimerism" refers to a small population of cells or DNA in one individual that derives from another genetically distinct individual. Cell traffic between mother and fetus during pregnancy has recently been found to result in long-term persistence of fetal cells (fetal microchimerism) in the mother and maternal cells in her progeny (maternal microchimerism). Microchimerism may also result from twin-twin transfer in utero. Although not formally proven, fetal microchimerism is presumed to persist after miscarriage and abortion. Theoretically, microchimerism could also derive from an older sibling transferred via the maternal circulation to the fetus of a later pregnancy.

2) Recent studies have investigated a potential role of naturally acquired fetal and maternal microchimerism in autoimmune diseases, including systemic sclerosis (scleroderma), thyroiditis, primary biliary cirrhosis (PBC), Sjoegren syndrome, systemic lupus erythematosus (SLE), dermatomyositis, and neonatal lupus syndrome. While lending support to the concept that microchimerism may contribute to some autoimmune diseases, studies have also shown that naturally acquired fetal and maternal microchimerism are common in healthy individuals.

3) Whereas the appreciation of naturally acquired microchimerism is relatively new, a more extensive literature has examined "iatrogenic chimerism" in hematopoietic cell transplantation (HCT), organ transplantation, and following blood transfusion. Iatrogenic chimerism in HCT can result in chronic graft-vs-host disease, a disorder with striking clinical similarities to autoimmune disease, including development of autoantibodies. The recent finding that healthy individuals often have low levels of maternal microchimerism may have relevance to prior studies in transplantation describing tolerance to organs mismatched for noninherited maternal HLA antigens. Microchimeric cells expressing tissue-specific markers have recently been reported in transplantation as well as in autoimmune disease, suggesting microchimeric cells may differentiate and thus could contribute to tissue repair or be a target in autoimmune disease. Recent findings in naturally acquired microchimerism reveal areas of common insight with iatrogenic microchimerism and suggest that detrimental and beneficial effects occur.

4) In summary: Recent studies indicate cells transfer between fetus and mother during pregnancy and can persist in both decades later. The presence within one individual of a small population of cells from another genetically distinct individual is referred to as "microchimerism". Naturally acquired microchimerism has recently been investigated in autoimmune diseases, including scleroderma, thyroiditis, primary biliary cirrhosis, Sjoegren syndrome, systemic lupus, dermatomyositis, and neonatal lupus. Iatrogenic chimerism has been investigated in transplantation and following blood transfusion. Considering findings of naturally acquired microchimerism along with iatrogenic microchimerism suggests microchimerism can have detrimental and/or beneficial effects in both settings. Recent identification of tissue-specific microchimerism either from naturally acquired or iatrogenic microchimerism (eg, cardiac myocytes) raises the possibility that microchimerism can be a target of autoimmunity or alternatively contribute to tissue repair.(1-5)

References (abridged):

1. Lo YMD, Lau TK, Chan LYS, et al. Quantitative analysis of the bi-directional fetomaternal transfer of nucleated cells and plasma DNA. Clin Chem. 2000;46:1301-1309

2. Nelson JL, Furst DE, Maloney S, et al. Microchimerism and HLA-compatible relationships of pregnancy in SSc. Lancet. 1998;351:559-562

3. Nelson JL. Maternal-fetal immunology and autoimmune disease: is some autoimmune disease auto-alloimmune or allo-autoimmune? Arthritis Rheum. 1996;39:191-194

4. Artlett CM, Smith JB, Jimenez, SA. Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis. N Engl J Med. 1998;338:1186-1191

5. Ohtsuka T, Miyamoto Y, Yamakage A, Yamazaki S. Quantitative analysis of microchimerism in systemic sclerosis skin tissue. Arch Dermatol Res. 2001;293:387-391

J. Am. Med. Assoc. http://www.jama.com

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CHIMERISM OF THE TRANSPLANTED HEART

In general, a "chimera" is any cell or organ or organism with genetic material from two or more genotypes (e.g., two or more species). In this context, a chimera is an organ or system with cells from two or more individuals of the same species, e.g., a condition that may result from transplantation of an organ from one individual into another followed by migration of cells into or out of the organ.

The following points are made by F. Quaini et al (New Engl. J. Med. 2002 346:5):

1) The interaction between donor and recipient cells after transplantation has received great attention in an attempt to identify the basis of rejection and graft-versus-host disease. Cell migration from the allograft to the recipient results "systemic chimerism", and cell migration from the host to the transplanted organ results in chimerism in the organ. Chimerism may be detected easily after sex-mismatched organ transplantation with the use of fluorescence in situ hybridization for the Y chromosome. Systemic chimerism may be recognized when a female host receives an organ from a male donor, and chimerism may be identified in an organ after the transplantation of the organ from a female donor into a male patient.

2) The origin and fate of recipient cells in the transplanted human heart are unknown. At present, there is no proof that chimerism leads to the generation of differentiated myocytes (muscle cells) and intact coronary artery branches. Experimental evidence points to the contribution of the cells of the host to neointimal thickening of intramural coronary vessels and transplant-related vascular pathology. But the formation of normal myocytes, arterioles, and capillaries has not been shown to occur in the grafted heart. Recent demonstration of the ability of primitive cells to mobilize and home to the infarcted heart have raised the possibility that undifferentiated cells may translocate from the recipient to the graft, contributing to ventricular remodeling. These cells, together with circulating endothelial and smooth muscle-cell progenitors, could colonize the new heart. Such a form of chimerism could regenerate myocardium (heart muscle) and sustain cardiac performance.

3) To test the above hypothesis, the authors studied male patients who received hearts from female donors. The authors report their results demonstrate a high level of cardiac chimerism caused by the migration of primitive cells from the recipient to the grafted heart. Putative stem cells and progenitor cells were identified in control myocardium and in increased numbers in transplanted hearts.

New Engl. J. Med. http://www.nejm.org

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