Is gene expression among women with rheumatoid arthritis dysregulated during a postpartum flare?

Matthew Wright; Mette K. Smed; J. Lee Nelson; Jørn Olsen; Merete L. Hetland; Vibeke Zoffmann; Damini Jawaheer

doi:10.1186/s13075-021-02418-w

Is gene expression among women with rheumatoid arthritis dysregulated during a postpartum flare?

Matthew Wright, Mette K. Smed, J. Lee Nelson, Jørn Olsen, Merete L. Hetland, Vibeke Zoffmann, Damini Jawaheer^*

^*Corresponding author for this work

Department of Clinical Medicine - Department of Clinical Epidemiology
Department of Molecular Biology and Genetics - Bioinformatics Research Centre (BiRC), Rigshospitalet

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

2 Citations (Scopus)

Abstract

Background: To evaluate our hypotheses that, when rheumatoid arthritis (RA) flares postpartum, gene expression patterns are altered compared to (a) healthy women, (b) RA women whose disease activity is low or in remission postpartum, and (c) pre-pregnancy expression profiles. Methods: Twelve women with RA and five healthy women were included in this pilot study. RA disease activity and postpartum flare were assessed using the Clinical Disease Activity Index (CDAI). Total RNA from frozen whole blood was used for RNA sequencing. Differential gene expression within the same women (within-group) over time, i.e., postpartum vs. third trimester (T3) or pre-pregnancy (T0), were examined, using a significance threshold of q < 0.05 and fold-change ≥ 2. Results: Nine of the women with RA experienced a flare postpartum (RA_Flare), while three had low disease activity or were in remission (RA_NoFlare) during that time frame. Numerous immune-related genes were differentially expressed postpartum (vs. T3) during a flare. Fold-changes in expression from T3 to postpartum were mostly comparable between the RA_Flare and healthy groups. At 3 months postpartum, compared to healthy women, several genes were significantly differentially expressed only among the RA_Flare women, and not among the RA_NoFlare women. Some of these genes were among those whose “normal” expression was significantly modulated postpartum, and the postpartum expression patterns were significantly altered during the RA flare. There were also some genes that were significantly differentially expressed in RA_Flare compared to both healthy and RA_NoFlare women, even though their expression was not significantly modulated postpartum. Furthermore, while postpartum expression profiles were similar to those at pre-pregnancy among healthy women, significant differences were found between those time points among the RA_Flare women. Conclusions: The large majority of gene expression changes between T3 and 3 months postpartum among RA women who flared postpartum reflected normal postpartum changes also seen among healthy women. Nonetheless, during a postpartum flare, a set of immune-related genes showed dysregulated expression compared to healthy women and women with RA whose disease activity was low or in remission during the same time frame, while other genes demonstrated significant differences in expression compared to RA pre-pregnancy levels.

Original language	English
Article number	30
Journal	Arthritis Research and Therapy
Volume	23
ISSN	1478-6354
DOIs	https://doi.org/10.1186/s13075-021-02418-w
Publication status	Published - Dec 2021

Keywords

Disease activity
Gene expression
Postpartum flare
Rheumatoid arthritis
RNA-seq

Access to Document

10.1186/s13075-021-02418-w

Cite this

@article{e44345fe434e4d398c119b961bdc1076,

title = "Is gene expression among women with rheumatoid arthritis dysregulated during a postpartum flare?",

abstract = "Background: To evaluate our hypotheses that, when rheumatoid arthritis (RA) flares postpartum, gene expression patterns are altered compared to (a) healthy women, (b) RA women whose disease activity is low or in remission postpartum, and (c) pre-pregnancy expression profiles. Methods: Twelve women with RA and five healthy women were included in this pilot study. RA disease activity and postpartum flare were assessed using the Clinical Disease Activity Index (CDAI). Total RNA from frozen whole blood was used for RNA sequencing. Differential gene expression within the same women (within-group) over time, i.e., postpartum vs. third trimester (T3) or pre-pregnancy (T0), were examined, using a significance threshold of q < 0.05 and fold-change ≥ 2. Results: Nine of the women with RA experienced a flare postpartum (RAFlare), while three had low disease activity or were in remission (RANoFlare) during that time frame. Numerous immune-related genes were differentially expressed postpartum (vs. T3) during a flare. Fold-changes in expression from T3 to postpartum were mostly comparable between the RAFlare and healthy groups. At 3 months postpartum, compared to healthy women, several genes were significantly differentially expressed only among the RAFlare women, and not among the RANoFlare women. Some of these genes were among those whose “normal” expression was significantly modulated postpartum, and the postpartum expression patterns were significantly altered during the RA flare. There were also some genes that were significantly differentially expressed in RAFlare compared to both healthy and RANoFlare women, even though their expression was not significantly modulated postpartum. Furthermore, while postpartum expression profiles were similar to those at pre-pregnancy among healthy women, significant differences were found between those time points among the RAFlare women. Conclusions: The large majority of gene expression changes between T3 and 3 months postpartum among RA women who flared postpartum reflected normal postpartum changes also seen among healthy women. Nonetheless, during a postpartum flare, a set of immune-related genes showed dysregulated expression compared to healthy women and women with RA whose disease activity was low or in remission during the same time frame, while other genes demonstrated significant differences in expression compared to RA pre-pregnancy levels.",

keywords = "Disease activity, Gene expression, Postpartum flare, Rheumatoid arthritis, RNA-seq",

author = "Matthew Wright and Smed, {Mette K.} and Nelson, {J. Lee} and J{\o}rn Olsen and Hetland, {Merete L.} and Vibeke Zoffmann and Damini Jawaheer",

note = "Funding Information: We are immensely grateful to the study subjects for their participation in the study. We acknowledge our gratitude towards Dr. Hanne Kj?rgaard for all her efforts in setting up the logistics for this study in Denmark; Dr. Kj?rgaard passed away in 2013. We also thank the leadership team at the Juliane Marie Center in Denmark for their support. The rheumatology departments at the following hospitals in Denmark facilitated collection of data and samples: Rigshospitalet (Glostrup), Odense Universitetshospital, Dansk Gigthospital (S?nderborg), Aarhus University Hospital (Skejby), and Regionshospitalet Viborg. We thank all members of our project team for making this work possible: Anne-Grethe Rasmussen, Charlotte Sch?n Frengler, Dorte Heide, Randi Petersen, Tove Thorup Rasmussen, Lone Thomasen, Britta Hvidberg Nielsen, Teresa Rozenfeld, Kirsten Junker, Lis Kastberg Schubert, Lis Lund, Jette Barlach, Helle Bendtsen, Helle Andersen, and Marjo Westerdahl for their contribution with data and sample collection; Rikke Godtkj?r Andersen, Mie Rams Rasmussen, Katrine Elmgaard Jensen, Pia Pedersen, Stine Birkelund, Louise Mielke, and Andreas Smed for management of data and samples. We also greatly appreciate valuable assistance provided by DANBIO personnel. Dr. Damini Jawaheer accepts responsibility for the integrity and validity of the data collected and analyzed. Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = dec,

doi = "10.1186/s13075-021-02418-w",

language = "English",

volume = "23",

journal = "Arthritis Research and Therapy",