Pregnancy Normalizes Immunity in Women with Rheumatoid Arthritis

BERLIN, When women with rheumatoid arthritis become pregnant, their immune systems appear to normalize, possibly explaining why they go into remission, researchers But after delivery a suite of genes involved in the innate and adaptive immune systems is over-expressed, compared with healthy women post-partum, according to Thomas Haupl, M.D., of Charité-University Medicine, and colleagues.
The changes appear to correspond to the remission in rheumatoid arthritis commonly seen during pregnancy, Dr. Haupl and colleagues reported in the October issue of Arthritis & Rheumatism.
In six pregnant women with rheumatoid arthritis and eight healthy pregnant controls, the researchers tested gene expression in peripheral blood mononuclear cells during the third trimester of pregnancy and 24 weeks after delivery.
All of the women had uncomplicated pregnancies and delivered healthy children after 36 weeks of gestation, the researchers said, and for all but one patient, disease activity was low during pregnancy. Accordingly, four of the six received no drugs during pregnancy.
Using microarray technology, the researchers looked for genes whose expression differed by at least 1.5 times in at least half of all pairwise comparisons among the participants.
Analysis found the fewest differences were among the healthy women, with 10 genes increased and 50 decreased in activity after delivery, compared with during pregnancy.
But notably, the researchers said, there were also few differences between pregnant rheumatoid arthritis patients and the pregnant healthy volunteers -- with 39 genes increased and 48 decreased in activity.
In contrast to what Dr. Haupl and colleagues called "subtle differences" during pregnancy, many more genes whose activity changed were found when comparing either patients and controls after delivery, or patients before and after delivery.
In the first case, the researchers found, the patients had 155 genes whose activity increased compared with the controls and 30 whose activity decreased.
In the second case, after delivery the patients had 997 genes whose activity increased, compared with levels during pregnancy, and 48 whose activity fell.
The researchers said analysis of 32 "immunologically relevant cellular pathways" showed additional activation of genes related to adhesion, migration, defense against pathogens, and cell activation, including Notch, phosphatidylinositol, mTOR, Wnt, and MAPK signaling.
Dr. Haupl and colleagues found that -- in both patients and controls -- monocyte gene activity increased during pregnancy, while lymphocyte activity was lower.
Monocyte activity fell after delivery in the controls, they found, but persisted in the patients, implying that "innate immune functions play an important role" in reactivation of disease after delivery.
But among the patients, lymphocyte gene activity was also increased after delivery, the researchers said, suggesting that adaptive immune system functions serve as "cofactors in the relapse."