BERLIN, Germany—New research sheds light on why rheumatoid arthritis (RA) tends to become reactivated in the postpartum period, after remaining dormant during pregnancy. The findings appear in Arthritis & Rheumatism.¹

“Molecular processes of inflammation in RA are suppressed during pregnancy, but become activated postpartum,” conclude researchers led by Thomas Häupl, MD, of Charité University Medicine in Berlin. “We hypothesize that monocytes are important effectors of relapse, and that interaction with recurring lymphocyte activity may be critical.”

The researchers generated transcriptomes of peripheral blood mononuclear cells (PBMCs) from RA patients and healthy women using transcription profiling during the third trimester and 24 weeks after delivery. They used signatures of highly purified immune cells as well as Kyoto Encyclopedia of Genes and Genomes pathway annotations as a reference for functional interpretation.

Only minor differences in gene expression in PBMCs during pregnancy were found between RA patients and controls. RA postpartum profiles, however, presented the most dominant changes.

In both controls and pregnant RA patients, lymphocyte gene activity dropped and monocyte gene activity increased during pregnancy. After delivery, monocyte activity decreased in controls but persisted in RA patients.

Further analysis of 32 immunologically relevant cellular pathways showed a significant additional activation of genes related to adhesion, migration, defense of pathogens, and cell activation. These genes included Notch, phosphatidylinositol, mTOR, Wnt, and MAPK signaling, in RA patients postpartum.

Both arms of immune system involved postpartum

“Our findings indicate that innate immune functions play an important role in postpartum reactivation of arthritis,” the study authors conclude. “However, this may depend not only on the monocyte itself, but also on the recurrence of lymphocyte functions postpartum and thus on a critical interaction between both arms of the immune system.”

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. “Thus, our data strongly suggest that molecular mechanisms involved in remission during pregnancy are very broad and extremely potent.”

Going forward, “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,” the study authors conclude.

Postpartum period important in many autoimmune diseases

“This is a pilot study, but it is a very interesting and promising approach for additional work,” said J. Lee Nelson, MD, a professor of rheumatology at the University of Washington in Seattle and a member of the clinical research division at the Fred Hutchinson Cancer Research Center in Seattle.

“The profile of RA female patients during pregnancy is not all that different from normal pregnant women, and that makes sense,” Dr. Nelson told MSKreport.com. “We think that improvement of RA during pregnancy is a side benefit of things that occur normally during pregnancy [such as] immune changes that enable the body to tolerate the fetus. The postpartum period provides a window of clear differences in a multitude of autoimmune both in terms of disease activity and new onset disease. It’s not just RA that flares during the postpartum period, lupus flares, multiple sclerosis flares, and new onset of autoimmune thyroid disease is pretty high in that period. Looking at postpartum period could hold the key to understanding autoimmunity.”

Reference

1. Häupl T, ?stensen M, Grützkau A, et al. Reactivation of rheumatoid arthritis after pregnancy. Increased phagocyte and recurring lymphocyte gene activity. Arthritis Rheum. 2008;58:2981-2992.