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Contempo Updates | Clinician's Corner

Microchimerism:  An Investigative Frontier in Autoimmunity and Transplantation

Kristina M. Adams, MD; J. Lee Nelson, MD
JAMA. 2004;291(9):1127-1131. doi:10.1001/jama.291.9.1127.
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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, Sjögren 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. Advances in this new frontier of research with varied and numerous implications for human health are summarized.

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Figures

Figure 1. Male Cell in Female Liver by Fluorescence In Situ Hybridization
Graphic Jump Location
White arrowhead indicates a male cell containing 1 Y chromosome (green) and 1 X chromosome (red) surrounded by female cells containing 2 X chromosomes in the liver specimen of a woman with systemic sclerosis (scleroderma) (magnification × 100). The Y chromosome–specific probe for DYZ1 was labeled with green fluorescent fluorescein-isothiocyanate–linked deoxyuridine 5-triphosphate. The X chromosome–specific probe for DXZ1 (centromere-associated) was labeled with red fluorescent cyanine-3–linked deoxyuridine 5-triphosphate. Nuclei are identified by a blue nuclear counterstain, 4′,6′-diamidino-2-phenylindole hydrochloride (DAPI) and analyzed by fluorescence microscopy with a triple-band filter specific for fluorescein, cyanin 3, and DAPI.
Figure 2. Maternal Cell With a Myocardial Tissue–Specific Phenotype in a Male Infant Heart by Fluorescence In Situ Hybridization and Concomitant Immunohistochemistry
Graphic Jump Location
A, Fluorescence microscopy, white arrowhead indicates a female cell (presumed of maternal origin) with 2 X chromosomes (red fluorescent dye) observed among male cells with 1 Y chromosome (green fluorescent dye) in the heart tissue of a male infant who died from congenital heart block associated with neonatal lupus syndrome (magnification × 100). The Y chromosome–specific probe for DYZ1 was labeled with green fluorescent fluorescein-isothiocyanate–linked deoxyuridine 5-triphosphate. The X chromosome–specific probe for DXZ1 (centromere-associated) was labeled with red fluorescent cyanine-3–linked deoxyuridine 5-triphosphate. Nuclei are identified by a blue nuclear counterstain, 4′,6′-diamidino-2-phenylindole hydrochloride (DAPI) and analyzed by fluorescence microscopy with a triple-band filter specific for fluorescein, cyanin 3, and DAPI. B, Light microscopy, black arrowhead indicates the same maternal cell as in A. The brown staining within the cytoplasm surrounding the female nucleus indicates sarcomeric α-actin expression, consistent with a cardiac myocyte phenotype. Immunohistochemistry was performed with antibodies to sarcomeric α-actin, a peroxidase development system, and developed with diaminobenzene (magnification ×100). Printed with permission from Anne Stevens, MD, PhD.

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