Dataset Information

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?ResultsNine 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.

SUBMITTER: Wright M

PROVIDER: S-EPMC7812735 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Wright Matthew M Smed Mette K MK Nelson J Lee JL Olsen Jørn J Hetland Merete L ML Zoffmann Vibeke V Jawaheer Damini D

Arthritis research & therapy 20210118 1

<h4>Background</h4>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.<h4>Methods</h4>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 fr ...[more]

PMID: 33461591

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Project description:IntroductionThe mechanism underlying the spontaneous improvement of rheumatoid arthritis (RA) during pregnancy and the subsequent postpartum flare is incompletely understood, and the disease course varies widely between pregnant RA patients. In pregnancy, total and free levels of cortisol increase gradually, followed by a postpartum decrease to prepregnancy values. The glucocorticoid receptor (GR) polymorphisms BclI and N363S are associated with relatively increased glucocorticoid (GC) sensitivity, whereas the 9β and ER22/23EK polymorphisms of the GR gene are associated with a relatively decreased GC sensitivity. We examined the relation between the presence of these GR polymorphisms and level of disease activity and disease course of RA during pregnancy and postpartum.MethodsWe studied 147 participants of the PARA study (Pregnancy-Induced Amelioration of Rheumatoid Arthritis study), a prospective study investigating the natural improvement during pregnancy and the postpartum flare in women with RA. Patients were visited, preferably before pregnancy, at each trimester and at three postpartum time points. On all occasions, disease activity was scored by using DAS28. All patients were genotyped for the GR polymorphisms BclI, N363S, 9β, and ER22/23EK and divided in groups harboring either polymorphisms conferring increased GC sensitivity (BclI and N363S; GC-S patients) or polymorphisms conferring decreased GC sensitivity (9β or 9β + ER22/23EK; GC-I patients). Data were analyzed by using a mixed linear model, comparing GC-S patients with GC-I patients with respect to improvement during pregnancy and the postpartum flare. The cumulative disease activity was calculated by using time-integrated values (area under the curve, AUC) of DAS28 in GC-I patients versus GC-S patients. Separate analyses were performed according to the state of GC use.ResultsGC-S patients treated with GC had a significantly lower AUC of DAS28 in the postpartum period than did GC-I patients. This difference was not observed in patients who were not treated with GCs. During pregnancy, GC-S and GC-I patients had comparable levels of disease activity and course of disease.ConclusionsDifferences in relative GC sensitivity, as determined by GR polymorphisms, are associated with the level of disease activity in the postpartum period in GC-treated patients, but they do not seem to influence the course of the disease per se.

Project description:BackgroundLittle 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).MethodsGlobal 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.ResultsA total of 1296 genes were differentially expressed between T3 and T0 among the 8 pregDASimproved women, 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 pregDASimproved and pregDASworse groups, 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 pregDASimproved women.ConclusionsIn 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.

Dataset Information

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

Background

Methods

Conclusions

Publications

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

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