Dr. Villiger has received consulting fees, speaking fees, and/or honoraria from Essex, Wyeth, Abbott, Pfizer, Roche, and Novartis (less than $10,000 each).
Rheumatoid Arthritis Clinical Studies
Reactivation of rheumatoid arthritis after pregnancy: Increased phagocyte and recurring lymphocyte gene activity
Article first published online: 29 SEP 2008
Copyright © 2008 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 58, Issue 10, pages 2981–2992, October 2008
How to Cite
Häupl, T., ØStensen, M., Grützkau, A., Radbruch, A., Burmester, G.-R. and Villiger, P. M. (2008), Reactivation of rheumatoid arthritis after pregnancy: Increased phagocyte and recurring lymphocyte gene activity. Arthritis & Rheumatism, 58: 2981–2992. doi: 10.1002/art.23907
- Issue published online: 29 SEP 2008
- Article first published online: 29 SEP 2008
- Manuscript Accepted: 20 JUN 2008
- Manuscript Received: 3 OCT 2007
- German Science Foundation. Grant Number: DFG grant HA-2267/2
- German Federal Ministry of Education and Research through the National Genome Research Network (Infection and Inflammation Network SIPAGE. Grant Number: 01GS0413
- European Union Sixth Framework Programme project AutoCure. Grant Number: 018661
- Swiss National Science Foundation. Grant Number: 1535-16-075
- Kurt and Senta Herrmann Foundation, Liechtenstein
Pregnancy is associated with reduced disease activity in rheumatoid arthritis (RA) and frequently with disease exacerbation after delivery. This study was undertaken to generate a systematic overview of the molecular mechanisms related to disease remission and postpartum reactivation.
Transcriptomes of peripheral blood mononuclear cells (PBMCs) were generated from RA patients and healthy women by transcription profiling during the third trimester and 24 weeks after delivery. For functional interpretation, signatures of highly purified immune cells as well as Kyoto Encyclopedia of Genes and Genomes pathway annotations were used as a reference.
Only minor differences in gene expression in PBMCs during pregnancy were found between RA patients and controls. In contrast, RA postpartum profiles presented the most dominant changes. Systematic comparison with expression signatures of monocytes, T cells, and B cells in healthy donors revealed reduced lymphocyte and elevated monocyte gene activity during pregnancy in patients with RA and in controls. Monocyte activity decreased after delivery in controls but persisted in RA patients. Furthermore, analysis of 32 immunologically relevant cellular pathways demonstrated a significant additional activation of genes related to adhesion, migration, defense of pathogens, and cell activation, including Notch, phosphatidylinositol, mTOR, Wnt, and MAPK signaling, in RA patients postpartum.
Our findings indicate that innate immune functions play an important role in postpartum reactivation of arthritis. 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.