Pregnancy-induced gene expression changes in vivo among women with rheumatoid arthritis: a pilot study

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Dana E Goin, Integrative Biology, University of California Berkeley, Berkeley, CA, USA, United States
  • Mette Kiel Smed, Juliane Marie Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Denmark
  • Lior Pachter, California Institute of Technology, Pasadena, CA 91125, USA, United States
  • Elizabeth Purdom, Integrative Biology, University of California Berkeley, Berkeley, CA, USA, United States
  • J Lee Nelson, University of Washington, Seattle Cancer Care Alliance, Seattle, WA, USA., United States
  • Hanne Kjærgaard, Juliane Marie Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Denmark
  • Jørn Olsen
  • Merete Lund Hetland, School of Pharmaceutical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, Denmark
  • Vibeke Zoffmann, Juliane Marie Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., School of Pharmaceutical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • ,
  • Bent Ottesen, Juliane Marie Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Denmark
  • Damini Jawaheer, University of California, San Francisco, San Francisco, CA, USA. djawaheer@chori.org., United States

BACKGROUND: Little is known about gene expression changes induced by pregnancy in women with rheumatoid arthritis (RA) and healthy women because the few studies previously conducted did not have pre-pregnancy samples available as baseline. We have established a cohort of women with RA and healthy women followed prospectively from a pre-pregnancy baseline. In this study, we tested the hypothesis that pregnancy-induced changes in gene expression among women with RA who improve during pregnancy (pregDASimproved) overlap substantially with changes observed among healthy women and differ from changes observed among women with RA who worsen during pregnancy (pregDASworse).

METHODS: Global gene expression profiles were generated by RNA sequencing (RNA-seq) from 11 women with RA and 5 healthy women before pregnancy (T0) and at the third trimester (T3). Among the women with RA, eight showed an improvement in disease activity by T3, whereas three worsened. Differential expression analysis was used to identify genes demonstrating significant changes in expression within each of the RA and healthy groups (T3 vs T0), as well as between the groups at each time point. Gene set enrichment was assessed in terms of Gene Ontology processes and protein networks.

RESULTS: A total of 1296 genes were differentially expressed between T3 and T0 among the 8 pregDASimprovedwomen, with 161 genes showing at least two-fold change (FC) in expression by T3. The majority (108 of 161 genes) were also differentially expressed among healthy women (q<0.05, FC≥2). Additionally, a small cluster of genes demonstrated contrasting changes in expression between the pregDASimprovedand pregDASworsegroups, all of which were inducible by type I interferon (IFN). These IFN-inducible genes were over-expressed at T3 compared to the T0 baseline among the pregDASimprovedwomen.

CONCLUSIONS: In our pilot RNA-seq dataset, increased pregnancy-induced expression of type I IFN-inducible genes was observed among women with RA who improved during pregnancy, but not among women who worsened. These findings warrant further investigation into expression of these genes in RA pregnancy and their potential role in modulation of disease activity. These results are nevertheless preliminary and should be interpreted with caution until replicated in a larger sample.

Original languageEnglish
JournalArthritis research & therapy
Volume19
Issue1
Pages (from-to)104
Number of pages8
ISSN1478-6362
DOIs
Publication statusPublished - 25 May 2017

    Research areas

  • Adult, Arthritis, Rheumatoid, Female, Gene Expression Profiling, Humans, Pilot Projects, Pregnancy, Pregnancy Complications, Transcriptome, Journal Article, RNA-seq, Rheumatoid arthritis, Type I interferon

See relations at Aarhus University Citationformats

ID: 121731303