Fetal cells may trigger autoimmune disease

Researchers got a jolt some years ago when they tested the blood of a young female laboratory technician. A powerful molecular technique detected the presence of genetic material from the Y, or male, chromosome. The researchers feared something had gone wrong with the test.

 Once they realized the technician was 6 weeks pregnant, however, that solved the mystery, recalls Diana W. Bianchi, a pediatric geneticist at the New England Medical Center in Boston. The test had homed in on male DNA in fetal cells that were circulating in the woman's bloodstream.

 That 1992 observation suggested that researchers could find a few fetal cells very early in a pregnancy. Then, in 1996, Bianchi's team made a dramatic discovery. Fetal cells can linger in the maternal bloodstream, sometimes for decades after childbirth.

 Now, Bianchi has hints that this biological legacy may be linked to an autoimmune disorder in the mother.

 After the 1996 report, the team wondered whether lingering fetal cells in the mother's bloodstream might, in some cases, incite her immune cells to attack her own tissue. The team focused on scleroderma, a sometimes deadly autoimmune disorder in which degeneration of skin, lungs, and internal organs occurs. Middle-aged women suffer most frequently from this disease.

 The team found male DNA circulating in the bloodstream of women with scleroderma who had given birth decades ago to at least one son. When the researchers looked at healthy women who had teenage or adult sons, however, they at first found no sign of fetal cells. Subsequent, more sensitive tests revealed small numbers of fetal cells in some of these women. Healthy women either don't have such cells or have few of them, Bianchi concludes.

 She reported the findings on July 21 at Press Week 1997, a meeting sponsored by the Jackson Laboratory and Johns Hopkins University and held in Bar Harbor, Maine.

 Male fetal cells aren't likely to be the only culprits in such diseases. The research team looked for male DNA because of the ease of finding the Y chromosome in a woman's blood, Bianchi says, but female fetal cells may also underlie autoimmune attacks.

 During the trauma of labor and delivery, hundreds of thousands of fetal cells surge into the mother's bloodstream, Bianchi says. The researchers believe that the immune system usually clears most of those cells from the mother's body. In some cases, however, large numbers of fetal cells persist. The mother's immune system then may recognize the cells as foreign and begin a blitz that eventually runs amok and leads to scleroderma or another autoimmune disorder, Bianchi speculates.

 The team now plans to turn its attention to other autoimmune disorders, such as Sjogren's syndrome. "There are a whole host of diseases that are much more common in women," Bianchi says. "Most of those diseases have been explained on the basis of hormonal differences." The new work hints at another mechanism, however, one that involves the lasting legacy of pregnancy, she says.

 Although the unpublished study demonstrates the existence of fetal cells in the blood of women with scleroderma, it doesn't prove that such cells directly lead to disease in the mother. Additional research must be done to discover whether the fetal cells or other factors actually kick off the damaging autoimmune reaction, comments David L. Valle of the Howard Hughes Medical Institute at Johns Hopkins Medical Institutions in Baltimore.

 The study raises some tantalizing possibilities for the treatment of autoimmune disorders in women, Valle says. If additional work confirms the notion that fetal cells trigger disease, then physicians might work to develop a treatment that would facilitate clearance of fetal cells at the time of delivery, he says. Such an approach might prevent the development of an autoimmune disorder decades later.