Published in Arthritis & Rheumatism, July, 2006
It has long been a mystery why women with rheumatoid arthritis (RA) often experience a remission during pregnancy, only to have the disease resume after their babies are born. Recently, a team of scientists at Fred Hutchinson Cancer Research Center in Seattle, WA, attempted to find an answer to why this happens, in hopes that any answers will open the door to new therapies for people with this chronic inflammatory disease.
The team measured the amount of DNA from the fetus present in the blood of 25 pregnant women with RA, assuming that if the DNA is present, the cells from which it came must be there as well. The quantity of the circulating fetal DNA was compared with the women’s disease activity during and after the pregnancy. They also questioned participants about their disease activity in the months before becoming pregnant.
They found that the more fetal DNA circulating in the mother’s blood, the lower her RA disease activity. Thus it appears that entry of fetal cells into the maternal circulation somehow changes the immune system in ways that benefit patients with RA. As the pregnancy progresses, continuous entry of fetal cells into the maternal circulation keeps disease activity low. Upon delivery, fetal DNA is cleared from the mother’s body. Ninety percent of patients who had improved during pregnancy had a disease recurrence within three or four months after delivery.
The scientists believe the main source of fetal DNA in the mother’s serum is from trophoblasts, a layer of cells that helps the embryo attach to the uterine wall and forms part of the placenta. Other investigators have found that trophoblasts shed HLA class II molecules, which may play a role in the development of RA.
Cells within the mother’s immune system capture both the maternal HLA molecules and the fetal HLA molecules and present them to T cells, a type of white blood cell that plays an essential role in immunity. When a woman has RA, her body does not recognize these maternal HLA molecules as self, and the immune system launches an attack, resulting in the disease. However, a mother’s body is programmed to accept and tolerate fetal molecules in order to make it possible for her to carry a child to term. Essentially, the presence of fetal HLA class II molecules halts the autoimmunity caused by the HLA class II molecules prior to pregnancy. The result is that the RA disease activity slows or stops during pregnancy.
“While much work remains to understand fully the reasons why RA is impacted by pregnancy, this study sheds light on the role fetal cells play in the mother’s immune system,” says John A. Hardin, MD, Chief Scientific Officer, Arthritis Foundation. “Hopefully, more investigators will continue to hunt for answers to these questions, which could result in important breakthroughs in the study of RA.”
Yan Z, Lambert NC, ØStensen M, et al. Prospective study of fetal DNA in serum and disease activity during pregnancy in women with inflammatory arthritis. Arthritis Rheum 2006;54:2069-73.