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Pregnancy-Induced Changes in Systemic Gene Expression among Healthy Women and Women with Rheumatoid Arthritis

Mittal, Anuradha and Pachter, Lior and Nelson, J. Lee and Kjærgaard, Hanne and Smed, Mette Kiel and Gildengorin, Virginia L. and Zoffmann, Vibeke and Hetland, Merete Lund and Jewell, Nicholas P. and Olsen, Jørn and Jawaheer, Damini (2015) Pregnancy-Induced Changes in Systemic Gene Expression among Healthy Women and Women with Rheumatoid Arthritis. PLOS ONE, 10 (12). Art. No. e0145204. ISSN 1932-6203. PMCID PMC4684291. doi:10.1371/journal.pone.0145204.

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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.

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Pachter, Lior0000-0002-9164-6231
Additional Information:© 2015 Mittal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: September 24, 2015; Accepted: November 30, 2015; Published: December 18, 2015. This work was supported in part by funds from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS,, USA (grant R21AR057931); and Gigtforeningen (, Denmark (grant R87-A1477-B512). Author DJ received the funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We are grateful to the study subjects for their participation in the study. The Rheumatology departments at the following hospitals in Denmark facilitated collection of data and samples: Rigshospitalet (Glostrup), Odense Universitetshospital, Kong Christian X's Gigthospital (Gråsten), Århus University Hospital NBG and Regionshospitalet Viborg. We thank Anne-Grethe Rasmussen, Charlotte Schön Frengler, Dorte Heide, Randi Petersen, Tove Thorup Rasmussen, Lone Thomasen, Britta Hvidberg Nielsen, Teresa Rozenfeldt, Kirsten Junker, Lis Kastberg Schubert, Lis Lund, and Jette Barlach for their contribution with data and sample collection, and Rikke Godtkjær Andersen, Mie Rasmussen and Tashnia Hossain for management of data and samples. We also greatly appreciate valuable assistance provided by Majbritt Norman Nielsen, and DANBIO personnel. Dr. Hanne Kjærgaard passed away before the submission of the final version of this manuscript. Dr. Damini Jawaheer accepts responsibility for the integrity and validity of the data collected and analyzed. Author Contributions: Conceived and designed the experiments: AM JLN HK NPJ JO DJ. Performed the experiments: HK MKS VZ DJ. Analyzed the data: AM LP VLG NPJ DJ. Contributed reagents/materials/analysis tools: AM LP HK MKS VZ MLH NPJ DJ. Wrote the paper: AM LP JLN MKS VLG VZ MLH NPJ JO DJ. Data Availability: Data are governed by Danish privacy laws. The authors are legally forbidden from publicly sharing data under the terms of their agreement with the Danish Data Protection Agency. Data are available upon request to the corresponding author, after approval is granted by the Danish Data Protection Agency. The authors have declared that no competing interests exist.
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Issue or Number:12
PubMed Central ID:PMC4684291
Record Number:CaltechAUTHORS:20170303-124807271
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Official Citation:Mittal A, Pachter L, Nelson JL, Kjærgaard H, Smed MK, Gildengorin VL, et al. (2015) Pregnancy-Induced Changes in Systemic Gene Expression among Healthy Women and Women with Rheumatoid Arthritis. PLoS ONE 10(12): e0145204. doi:10.1371/journal.pone.0145204
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ID Code:74702
Deposited By: George Porter
Deposited On:03 Mar 2017 21:37
Last Modified:11 Nov 2021 05:29

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