SEATTLE -- Circulating fetal cells may account for why rheumatoid arthritis tends to improve or even disappear during pregnancy, according to researchers here.
SEATTLE, July 10 -- Circulating fetal cells may account for why rheumatoid arthritis tends to improve or even disappear during pregnancy, according to researchers here.
For every doubling of fetal DNA in a pregnant woman's bloodstream, the likelihood of her arthritis improving increased by 20%, said Zhen Yan, M.D., Ph.D., of the Fred Hutchinson Cancer Research Center, and colleagues, reported in the July issue of Arthritis & Rheumatism.
The study included 25 pregnant women. Of these, 19 had adult onset RA and six had juvenile idiopathic arthritis. Serum levels of fetal DNA were measured at least three times during the pregnancy and about three months after delivery. The women's disease status was assessed each trimester and three to four months after giving birth.
A large proportion of fetal cells in a pregnant woman's bloodstream come from placental cells that have died off as the placenta grows, the researchers noted.
Levels of serum fetal DNA increased with advancing gestation, reaching a median of 24 gE/mL (range 0 to 334) in the first trimester, 61 gE/mL (range 0 to 689) in the second trimester, and 199 gE/mL (range 0 to 2,576) in the third trimester.
Of the 25 women, 21 had improvement or remission of disease, including all of the patients with juvenile idiopathic arthritis. The researchers reported an inverse relationship between fetal DNA levels and disease activity. For every doubling of fetal DNA levels, the chances of arthritis improving was 1.20 (95% confidence interval = 1.1 to 1.3; P<.001).
However, for four women in the study, fetal DNA levels increased little or not at all. In this group, fetal DNA was undetectable in two women and reached a median of only 78 gE/mL in the third trimester for the other two. These women did not have significant reduction in disease activity during pregnancy.
The study did not attempt to identify a biological mechanism underlying its findings. However, the researchers speculated that snippets of human leukocyte antigen (HLA) from the fetal DNA might be picked up by antigen-presenting cells of the mother's immune system, such as dendritic cells.
Presentation of fetal HLA to the maternal immune system "is likely to have immunologic effects that may reasonably be anticipated to also affect autoimmunity in RA patients, for example by the induction of regulatory T cells or by altering the maternal peripheral T-cell repertoire," the investigators said.
"In summary, serum fetal DNA concentration increased throughout gestation and was effectively cleared after delivery, with an inverse correlation observed between changes in fetal DNA levels and arthritis activity," the investigators said.
"Whether the dynamic changes in fetal DNA reflect the potential for immune modulation of maternal arthritis, are a result of disease activity changes, or are not causally related cannot be determined from these studies," they added.
However, if future research proved that fetal DNA modulated the maternal immune system, "further studies could generate new therapeutic strategies for RA," they said.