November 10, 2010 1 Comment
When you’re in utero, you’re protected from the outside world, connected to it only via the placenta, which is supposed to keep you and your mother separated. Separation is generally a good thing because you are foreign to your mother, and she is foreign to you. In spite of the generally good defenses, however, a little bit of you and a little bit of her cross the barrier. Scientists have recently found that when that happens, you often end up toting a bit of mom around for decades, maybe for life.
The presence of cells from someone else in another individual is called microchimerism. A chimera in mythology was a beast consisting of the parts of many animals, including lion, goat, and snake. In genetics, a chimera carries the genes of some other individual along with its own, perhaps even the genes of another species. In microchimerism, we carry a few cells from someone else around with us. Most women who have been pregnant have not only their own cells but some cells from their offspring, as well. I’m probably carrying around cells from each of my children.
Risks and benefits of sharing
Microchimerism can be useful but also carries risks. Researchers have identified maternal cells in the hearts of infants who died from infantile lupus and determined that the babies had died from heart block, partially from these maternal cells that had differentiated into excess heart muscle. On the other hand, in children with type 1 diabetes, maternal cells found in the pancreatic islets appear to be responding to damage and working to fix it.
The same good/bad outcomes exist for mothers who carry cells from their children. There has long been an association between past pregnancy and a reduced risk of breast cancer, but why has been unclear. Researchers studying microchimerism in women who had been pregnant found that those without breast cancer had fetal microchimerism at a rate three times that of women who with the cancer.
Microchimerism and autoimmunity
Autoimmune diseases develop when the body attacks itself, and several researchers have turned to microchimerism as one mechanism for this process. One fact that led them to investigate fetal microchimerism is the heavily female bias in autoimmune illness, suggesting a female-based event, like pregnancy. On the one hand, pregnancy appears to reduce the effects of rheumatoid arthritis, an autoimmune disorder affecting the joints and connective tissues. On the other hand, women who have been pregnant are more likely to develop an autoimmune disorder of the skin and organs called scleroderma (“hard skin”) that involves excess collagen deposition. There is also a suspected association between microchimerism and pre-eclampsia, a condition in pregnancy that can lead to dangerously high blood pressure and other complications that threaten the lives of mother and baby.
Human leukocyte antigen (HLA)
The autoimmune response may be based on a similarity between mother and child of HLA, immune-related proteins encoded on chromosome 6. This similarity may play a role in the immune imbalances that lead to autoimmune diseases; possibly because the HLAs of the mother and child are so similar, the body clicks out of balance with a possible HLA excess. If they were more different, the mother’s immune system might simply attack and destroy fetal HLAs, but with the strong similarity, fetal HLAs may be like an unexpected guest that behaves like one of the family.
Understanding the links between microchimerism and disease is the initial step in exploiting that knowledge for therapies or preventative approaches. Researchers have already used this information to predict the development of a complication in stem cell transplant called “graft-versus-host disease” (GVH). In stem cell transplants, female donors with previous pregnancies are more associated with development of GVH because they are microchimeric. Researchers have exploited this fact to try to predict whether or not there will be an early rejection of a transplant in kidney and pancreas organ transplants.
(Photo courtesy of Wikimedia Commons and photographer Ferdinand Reus).