Influence of pregnancy on the adipocytokine and peroxisome proliferator-activated receptor pathways in peripheral blood mononuclear cells from healthy donors and rheumatoid arthritis patients.
OBJECTIVE
To identify candidate genes that are regulated by human pregnancy and have the potential to modulate rheumatoid arthritis (RA) disease activity.


METHODS
Peripheral blood mononuclear cells (PBMCs) from healthy pregnant volunteers were analyzed using Affymetrix GeneChips at 4 time points (during the first, second, and third trimesters and 6 weeks postpartum). Based on the GeneChip data, target genes were further analyzed via real-time quantitative polymerase chain reaction (qPCR) using PBMCs from healthy controls and RA patients. In order to determine the cellular source of the candidate gene messenger RNA (mRNA), monocytes and lymphocytes from healthy controls and RA patients were positively selected using magnetic beads, and their mRNA was analyzed by qPCR.


RESULTS
One-way analysis of variance identified 1,286 mRNAs that were differentially expressed with regard to the 4 time points. The changes became more pronounced as pregnancy progressed, and they were reversed postpartum. A subsequent pathway analysis suggested a regulatory role of pregnancy on the adipocytokine pathway as well as on the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Of 19 preselected candidate genes, AKT3, SOCS3, FADS2, STAT1, and CD36 proved to be differentially regulated by pregnancy. In samples from RA patients, the differences were concordant with those in healthy controls but more pronounced. Both T lymphocytes and monocytes contributed to the regulated expression of these genes.


CONCLUSIONS
Our findings indicate that normal human pregnancy leads to changes in the expression of several molecular pathways in PBMCs, which are reversed postpartum. Changes in RA patients, although concordant, exceed the levels observed in healthy controls. Genes of the adipocytokine and PPAR signaling pathways qualify as candidates for the modulation of RA disease activity during pregnancy.
University Hospital and University of Bern, Bern, Switzerland.
Janine
J
Weix
Frauke
F
Förger
Thomas
T
Häupl
Daniel
D
Surbek
Monika
M
Østensen
Peter M
PM
Villiger
D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D054392:Adipokines; D047492:Peroxisome Proliferator-Activated Receptors