Reactivation of rheumatoid arthritis after pregnancy: increased phagocyte and recurring lymphocyte gene activity

Häupl, Thomas; Østensen, Monika; Grützkau, Andreas; Radbruch, Andreas; Burmester, Gerd-R; Villiger, Peter M (2008). Reactivation of rheumatoid arthritis after pregnancy: increased phagocyte and recurring lymphocyte gene activity. Arthritis & rheumatism, 58(10), pp. 2981-92. Hoboken, N.J.: Wiley-Blackwell 10.1002/art.23907

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OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology

UniBE Contributor:

Oestensen, Monika Elisabeth and Villiger, Peter

ISSN:

0004-3591

ISBN:

18821679

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:03

Last Modified:

04 May 2014 23:19

Publisher DOI:

10.1002/art.23907

PubMed ID:

18821679

Web of Science ID:

000260024400008

URI:

https://boris.unibe.ch/id/eprint/27509 (FactScience: 108182)

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