RESEARCH - Reactivation of RA after pregnancy: increased phagocyte and recurring lymphocyte gene activity

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Arthritis Rheum. 2008 Sep 29;58(10):2981-2992.

Reactivation of rheumatoid arthritis after pregnancy: Increased

phagocyte and recurring lymphocyte gene activity.

Häupl T, Ostensen M, Grützkau A, Radbruch A, Burmester GR, Villiger PM.

Charité-University Medicine, Berlin, Germany.

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.

PMID: 18821679

http://www.ncbi.nlm.nih.gov/pubmed/18821679

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