Reactivation of Rheumatoid Arthritis After Pregnancy

Arthritis & Rheumatism. 2008;58(10):2981-2992. 

The symptoms of rheumatoid arthritis (RA) in pregnant women typically diminish or disappear, only to return within three months after delivery. A new study exploring gene expression activity reveals changes in immune system cells that help explain this phenomenon. The study was published in the October issue of Arthritis & Rheumatism (

Led by Thomas Häupl of Charité-University Medicine in Berlin and Peter Villiger of Inselspital University Hospital in Bern, researchers used expression profiling, which measures the activity of large numbers of genes to create a global view of cellular function, to analyze the gene profiles of six pregnant women with RA and eight healthy controls in the third trimester of pregnancy and 24 weeks after delivery. Using blood samples, the researchers were able to examine changes in different types of immune cells largely in the absence of medication, an unusual opportunity in patients with this disease.

The results of this new bioinformatic approach showed that in the third trimester, the five women with RA who had low disease activity had a gene expression profile similar to the healthy pregnant women. After delivery, however, the RA patients had a broad panel of differentially expressed genes than when they were pregnant. The study also showed an additional activation of genes related to processes in both the innate and the adaptive immune response in the RA women. The innate immune system is the body's first line of defense in response to infection, while the adaptive immune system, which is activated by the innate immune system, is composed of highly specialized cells that have the ability to recognize and remember specific pathogens.

The fact that there were only minor differences in the gene expression profiles between the two groups of women "suggests that molecular pathologic mechanisms of inflammation are reduced corresponding to the clinical remission in late pregnancy," according to the authors. Interestingly, although the profiles of the RA patients were much different following delivery than they were during the third trimester, the clinical indications of disease activity did not show the same consistent change. The authors suggest that this may be because the molecular markers may reflect subclinical disease activity that is not manifested in observable symptoms. "Thus, our data strongly suggest that molecular mechanisms involved in remission during pregnancy are very broad and extremely potent," they note.

The authors also analyzed purified immune cells that had been extracted from the blood samples obtained in the study. They found an increase in phagocyte- and a decrease in lymphocyte-related gene activity in healthy pregnant women compared with samples obtained following delivery. These results confirm previous studies suggesting that innate immune cells (phagocytes, for example) are more active during pregnancy and may thereby compensate for the suppression of the adaptive immune system (to which lymphocytes belong) that is necessary to tolerate the fetus.

Analysis of postpartum RA samples showed an elevation of monocyte-related transcripts compared to the healthy controls, which suggests an important role of the innate immune processes in RA relapse, according to the authors. But the fact that lymphocyte-related genes also increased in RA patients after delivery indicates that the recurrence of adaptive immune functions also plays a role in relapse.

According to the authors, the study suggests that monocytes may play an important role in RA relapse following pregnancy and that their interaction with recurring lymphocyte activity may be critical. They conclude: "Extended functional studies and detailed analyses at different time points after pregnancy are needed to confirm these hypotheses and to further improve our knowledge about this highly interesting period of immunologic readjustment."



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