title: Pregnancy-Induced Changes in Systemic Gene Expression among Healthy Women and Women with Rheumatoid Arthritis.
abstract: BACKGROUND
  Pregnancy induces drastic biological changes systemically, and has a beneficial effect on some autoimmune conditions such as rheumatoid arthritis (RA). However, specific systemic changes that occur as a result of pregnancy have not been thoroughly examined in healthy women or women with RA. The goal of this study was to identify genes with expression patterns associated with pregnancy, compared to pre-pregnancy as baseline and determine whether those associations are modified by presence of RA.
  
  
  RESULTS
  In our RNA sequencing (RNA-seq) dataset from 5 healthy women and 20 women with RA, normalized expression levels of 4,710 genes were significantly associated with pregnancy status (pre-pregnancy, first, second and third trimesters) over time, irrespective of presence of RA (False Discovery Rate (FDR)-adjusted p value<0.05). These genes were enriched in pathways spanning multiple systems, as would be expected during pregnancy. A subset of these genes (n = 256) showed greater than two-fold change in expression during pregnancy compared to baseline levels, with distinct temporal trends through pregnancy. Another 98 genes involved in various biological processes including immune regulation exhibited expression patterns that were differentially associated with pregnancy in the presence or absence of RA.
  
  
  CONCLUSIONS
  Our findings support the hypothesis that the maternal immune system plays an active role during pregnancy, and also provide insight into other systemic changes that occur in the maternal transcriptome during pregnancy compared to the pre-pregnancy state. Only a small proportion of genes modulated by pregnancy were influenced by presence of RA in our data.
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California, United States of America.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Mittal
authors.affiliation: Department of Mathematics, University of California, Berkeley, California, United States of America.
authors.forename: Lior
authors.initials: L
authors.lastname: Pachter
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.|University of Washington, Seattle, Washington, United States of America.
authors.forename: J Lee
authors.initials: JL
authors.lastname: Nelson
authors.affiliation: Juliane Marie Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Kjærgaard
authors.affiliation: Juliane Marie Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Mette Kiel
authors.initials: MK
authors.lastname: Smed
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California, United States of America.
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Gildengorin
authors.affiliation: Juliane Marie Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Vibeke
authors.initials: V
authors.lastname: Zoffmann
authors.affiliation: DANBIO Registry and Copenhagen Centre for Arthritis Research, Centre for Rheumatology and Spine Diseases VRR, Rigshospitalet, Copenhagen, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Merete Lund
authors.initials: ML
authors.lastname: Hetland
authors.affiliation: School of Public Health, University of California, Berkeley, California, United States of America.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Jewell
authors.affiliation: School of Public Health, University of California Los Angeles, Los Angeles, California, United States of America.|Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jørn
authors.initials: J
authors.lastname: Olsen
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California, United States of America.
authors.forename: Damini
authors.initials: D
authors.lastname: Jawaheer
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D064368:Healthy Volunteers; D006801:Humans; D011247:Pregnancy / Q000235:genetics*; D017423:Sequence Analysis, RNA / Q000379:methods*