Presentation: Reactivation of Rheumatoid Arthritis after Pregnancy is Accompanied by Increased Phagocyte and Recurring Lymphocyte Gene Activity in the Peripheral Blood (2007)

823 Reactivation of Rheumatoid Arthritis after Pregnancy is Accompanied by Increased Phagocyte and Recurring Lymphocyte Gene Activity in the Peripheral Blood

Introduction: Activity of rheumatoid arthritis (RA) is known to be reduced during pregnancy, but exacerbates after delivery.
Objective: To characterize molecular changes in peripheral blood during and after pregnancy in RA patients compared to healthy women before and after delivery.
Methods: Gene expression profiles were determined by Affymetrix HG-U133A array hybridization of PBMC derived from 6 RA patients and 7 healthy women (ND) during the 3. trimester of pregnancy and 24 weeks after delivery. Array analysis was performed using standard software packages (GCOS, RMA). Data were compared with reference profiles of highly purified CD14+ peripheral blood monocytes, CD4+ and CD8+ T-cells, CD19+ B-cells, CD56+ NK-cells and CD15+ granulocytes of healthy donors. For functional interpretation pathway definitions of KEGG were applied.
Results:
PBMC transcription profiles revealed group specific expression patterns with most differences in RA post partum compared to RA during pregnancy or ND post partum. Comparison with reference profiles of purified cell types identified a broad panel of differentially expressed genes that were related to a shift in cellular composition. Healthy women presented a decrease in monocyte profile components and an increase in profile components of all lymphocyte populations after delivery. In contrast, elevated monocyte related profile components persisted in RA after pregnancy and were correlated with disease activity. Systematic analysis of 32 KEGG pathways including 1791 genes confirmed the shift in cell type specific pathways but also uncovered increased gene activity in RA post partum in pathways related to cell activation (phosphatidylinositol pathway) cell growth (cell cycle, mTOR signaling), differentiation (Notch signaling), adhesion (focal adhesion, adherens junction) and migration (leukocyte transendothelial migration). In particular, genes of the TLR, MAPK, and WNT signaling pathways, the cytokines IL8 and IL1b as well as chemokine receptors CCR1, CCR9 and CXCR4 were found activated. Adhesion and migration related processes and several signaling pathways correlated with disease activity.
Conclusion: The high activity of phagocyte associated genes after pregnancy suggests a critical role of innate immunity in the phase of disease reactivation. The increase in lymphocytes and related cell activation pathways indicates an important contributory role of theses cells in disease flare. It also demonstrates a suppression of the adaptive immune response during pregnancy. Collectively, our data are in agreement with current therapeutic concepts which on one hand target innate immune processes such as neutralization of TNF, but also the adaptive immune system by depletion of B lymphocytes or inhibition of monocyte-T cell interaction.

 T. Haeupl, None; M. Oestensen, None; A. Gruetzkau, None; A. Radbruch, None; G. Burmester, None; P. Villiger, None.