The rheumatoid arthritis gene expression signature among women who improve or worsen during pregnancy: A pilot study

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Objective. To assess whether gene expression signatures associated with rheumatoid arthritis (RA) before pregnancy differ between women who improve or worsen during pregnancy, and to determine whether these expression signatures are altered during pregnancy when RA improves or worsens. Methods. Clinical data and blood samples were collected before pregnancy (T0) and at the third trimester (T3) from 11 women with RA and 5 healthy women. RA disease activity was assessed using the Clinical Disease Activity Index (CDAI). At each timepoint, RA-associated gene expression signatures were identified using differential expression analysis of RNA sequencing profiles between women with RA and healthy women. Results. Of the women with RA, 6 improved by T3 (RAimproved), 3 worsened (RAworsened), and 2 were excluded. At T0, mean CDAI scores were similar in both groups (RAimproved 11.2 ± 9.8; RAworsened 13.8 ± 6.7; Wilcoxon rank-sum test: P = 0.6). In the RAimproved group, 89 genes were differentially expressed at T0 (q < 0.05 and fold change ≥ 2) compared to healthy women. When RA improved at T3, 65 of 89 (73%) of these genes no longer displayed RA-associated expression. In the RAworsened group, a largely different RA gene expression signature (429 genes) was identified at T0. When RA disease activity worsened at T3, 207 of 429 (48%) genes lost their differential expression, while an additional 151 genes became newly differentially expressed. Conclusion. In our pilot dataset, pre-pregnancy RA expression signatures differed between women who subsequently improved or worsened during pregnancy, suggesting that inherent genomic differences may influence how pregnancy affects disease activity. Further, these RA signatures were altered during pregnancy as disease activity changed.

OriginalsprogEngelsk
TidsskriftJournal of Rheumatology
Vol/bind48
Udgave nummer7
Sider (fra-til)985-991
Antal sider7
ISSN0315-162X
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
This work was supported in part by funds from the National Institutes of Arthritis, Musculoskeletal and Skin Diseases, USA (Grants R21AR057931 and R01AR073111); Gigtforeningen, Denmark (Grant R87-A1477-B512); the Juliane Marie Center, Rigshospitalet, Denmark; and a private donor. These funders did not have any role in conducting this study or in the interpretation and reporting of results. 1A. Pathi, BS, M. Wright, MS, Staff Research Associate II, Children’s Hospital Oakland Research Institute, Oakland, California, USA; 2M.K. Smed, RM, Study Coordinator, Juliane Marie Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 3J.L. Nelson, MD, Professor, Fred Hutchinson Cancer Research Center, and University of Washington, Seattle, Washington, USA; 4J. Olsen, MD, PhD, Professor, University of California Los Angeles, Los Angeles, California, USA, and Aarhus University Hospital, Aarhus, Denmark; 5M.L. Hetland, DMSc, Professor, DANBIO Registry and Copenhagen Centre for Arthritis Research, Centre for Rheumatology and Spine Diseases VRR, Rigshospitalet, Copenhagen, and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 6V. Zoffmann, RN, PhD, Professor, Juliane Marie Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, and Department of Public Health, University of Copenhagen, Copenhagen, Denmark; 7D. Jawaheer, PhD, Associate Scientist, Children’s Hospital Oakland Research Institute, Oakland, and University of California San Francisco, San Francisco, California, USA. AP and MW contributed equally to this work. The authors declare no conflicts of interest. Address correspondence to Dr. D. Jawaheer, UCSF Benioff Children’s Hospital Oakland, Children’s Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA. Email: Damini.Jawaheer@ucsf.edu. Accepted for publication December 3, 2020.

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Copyright © 2021 The Journal of Rheumatology. All rights reserved.

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