You may carry cells from siblings, aunts and uncles

YOUR siblings may be closer to you than you thought. Male cells have been found in the umbilical cord blood of baby girls with older brothers, suggesting that the transfer of cells between mother and baby may be more extensive than previously imagined. Indeed, all of us may be walking chimeras.

Previous studies have shown that cells from both mother and fetus can cross the placenta during pregnancy, and survive for decades in the skin, liver, brain and spleen - a phenomenon called fetal microchimerism. There is even evidence that fetal cells may repair damage to the mother's heart during pregnancy.

Other studies have hinted that fetal cells might contribute to autoimmune disease, prompting speculation that fetal cells disperse more widely, possibly passing between siblings and even across generations.

To investigate this, Miranda Dierselhuis of Leiden University Medical Center in the Netherlands and her colleagues analysed umbilical cord blood from 23 newborn girls, 17 of whom had older brothers. In a subset of the samples, they looked for immune cells directed against the male Y chromosome.

Of the 12 girls in the subset with elder brothers, 11 had cord blood containing immune cells against the Y chromosome, suggesting that male cells had somehow crossed the placenta from the mother - presumably entering her body from a male fetus during an earlier pregnancy. In some of the girls, DNA testing revealed direct evidence of male cells in the cord blood (Blood, DOI: 10.1182/blood-2012-02-410571).

"We may be more microchimeric than we imagined," says Dierselhuis, although she cautions that they haven't yet confirmed the source of the male cells.

Curiously, small numbers of male cells were also detected in one of the girls with no older brother, raising the possibility that these cells were from her uncle, passing to her mother during her grandmother's pregnancy. Another possibility is that they originated from an earlier miscarriage of which the mother was unaware.

"It shows just how ubiquitous the exchange of these cells is," says Hilary Gammill of the Fred Hutchinson Cancer Research Center in Seattle. "We used to think of the placenta as a complete barrier."

Last year, Gammill detected cells in the blood of pregnant women that came from their mothers - the grandmother of their fetus. The number of the cells increased as the pregnancies progressed (PLoS One, DOI: 10.1371/journal.pone.0024101).

"We think the mother's cells shape the ability of the developing immune system to learn tolerance," Gammill says. "We wonder if the grandmother's cells are continuing that education process in some way."

The discovery of even wider transfer of cells between siblings and across generations raises the possibility that these cells may influence the course of health or disease in all of us. Several diseases including asthma, type 1 diabetes and certain cancers are less common in younger siblings. "Even in small numbers, some of these cells have stem-like properties, so I think they could influence health," says Gammill.

Meanwhile, an autoimmune disease called scleroderma - which causes hardening of the skin and blood vessels - has also been linked to the presence of fetal cells in the blood, and seems to be more common in younger siblings. "The further you are down the line in birth order, the greater the risk," says Maureen Mayes at the University of Texas in Houston, who has studied the phenomenon (Arthritis Care and Research, DOI: 10.1002/acr.20096). "Multi-fetal microchimerism is one possible explanation," she says.

And Christoph Bucher of the University of Minnesota in Minneapolis reported in 2007 that stem-cell transplants from cord blood between siblings for various types of blood disease appeared to be more successful if the cells came from younger siblings. This hints that a level of tolerance had already developed between donor's and receiver's cells (Blood, DOI: 10.1182/blood-2007-02-076257). Previously it was assumed that cord blood was immunologically naive, but Dierselhuis's study may help to explain this phenomenon.

However, Bucher is cautious about whether the new study will have any immediate clinical impact. "It's a fascinating idea but it's not something that could be exploited clinically at this stage," he says. "More detailed studies are needed to show conclusively that sibling A is in the cord blood of sibling B."

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