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Another likely source of Mc, while not yet reported, is from an older sibling or previous pregnancy of the mother, because the mother could pass cells to the fetus of a subsequent pregnancy.
Both maternal and fetal origin Mc have been identified in different cell types and in multiple lipotesi del male in humans, sometimes in normal tissues and in a variety of diseases lipotesi del male 27 ].
Some approaches to Mc testing lipotesi del male summarized in Text box 1 [ 289 ]. Whether Mc has a beneficial, neutral or adverse lipotesi del male on the recipient probably depends on a number of factors including the origin of the Mc, type of cells acquired, time elapsed since Mc acquisition and age of the recipient.
Here we summarize current knowledge regarding naturally acquired Mc in health and disease, with emphasis on autoimmune disease and human studies. Text Box 1 Approaches to identify and characterize Mc Mc is usually evaluated by testing for either microchimeric DNA or microchimeric cells [reviewed in 2 ].
In the former approach, DNA is extracted from peripheral blood or tissues and assayed for a genetic polymorphism the test subject does not have. The most common DNA-based approach is testing for male DNA in a female as a marker for presumed prior pregnancy with a male fetus.
Maternal Mc can be identified with DNA-based techniques, although the approach is more complex as studies must first be conducted to identify a suitable genetic polymorphism of the mother that the test subject does not have [ 7 ]. To evaluate microchimeric cells, fluorescence in situ hybridization FISH is most often employed using X- and Y-chromosome specific probes.
This approach is suitable for identifying lipotesi del male cells 2 X-signals in a male 1 X and 1 Y-signal or male cells in a female. An lipotesi del male approach that is not limited to Mc that is sex mismatched, involves targeting other genetic polymorphisms in tissue specimens [ 8 ].
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A promising technique that was recently reported combines automatic retrieval of single microchimeric cells by laser microdissection and on-chip multiplex PCR for DNA fingerprint analysis [ 9 ].
Maternal microchimerism That maternal Mc can persist into adult life in immunocompetent adults was initially described in peripheral blood [ 3 ]. A systematic investigation of lipotesi del male Mc in normal human tissues is not available, however, maternal Mc has been detected in apparently normal tissues in the fetus, neonate, children and adults.
In second trimester fetuses the thymus, lung, heart, pancreas, liver, spleen, kidney, adrenal gland, ovary, testis and brain had maternal Mc [ 10 ]. In newborns and infants who had anomalies, aneuploidy or infection, the thymus, lung, pancreas, liver, thyroid and skin had maternal Mc [ 1112 ].
Maternal Mc was lipotesi del male in heart and skeletal muscle of some children without and with autoimmune disease [ 13 — 15 ].
The presence of maternal Mc as differentiated organ-specific cells was initially reported in children with the passively acquired autoimmune disease, neonatal lupus; female cardiac myocytes presumed maternal were identified in male infants who died from heart block [ 13 ].
Differentiated maternal cells in organs have also been found in the absence of autoimmune disease. In the male pancreas, insulin-positive female islet cells, lipotesi del male identified in non-diabetic and diabetic patients [ 1617 ].
Significant lipotesi del male differences of maternal Mc are frequently observed in autoimmune diseases, as discussed below, but it is evident that maternal cells can contribute to the overall body architecture even in healthy individuals.
The Otherness of Self: Microchimerism in Heath and Disease
Maternal Mc has functional consequences in her progeny. In experimental lipotesi del male, maternal Mc resulted in lipotesi del male of IL-2 in Il2 knockout mice [ 21 ]. Most lymph nodes of 2nd trimester fetuses contained maternal Mc and when lymph node cultures were depleted of T regulatory cells Tregfetal T cell response to maternal cells increased significantly, indicating fetal Treg-mediated suppression of anti-maternal T cell responses [ 22 ].
Moreover, Treg-mediated suppression to maternal, but not paternal alloantigens, was demonstrated up to the age of 17 in some children [ 22 ].
Further evidence that maternal Mc has long-term functional consequences comes from transplantation studies.