Pre-pregnant gene expression signatures can be potential biomarkers to predict perinatal outcomes of RA

Rheumatoid arthritis (RA) affects 1% of the adult population worldwide and is three times more common among women. Women diagnosed with RA who are planning to conceive often face several challenges, such as the risk of disease flare-ups and the teratogenic effects on the offspring. During pregnancy, around 50 to 70% of women with RA experience an improvement in their condition, while some may experience worsening of the disease. Now, scientists at Northwestern Medicine have identified pre-pregnancy gene expression signatures that can predict the RA disease outcomes during pregnancy.

The study included both healthy women and women of Danish descent with RA who were planning to conceive and were part of a prospective pregnancy cohort in Denmark. The researchers analyzed gene expression levels using samples collected before pregnancy from 19 women with RA and 13 healthy women. Among the 19 women with RA, 14 showed significant improvement in their disease, while 5 experienced worsening during pregnancy. The weighted gene co-expression network analysis revealed a co-expression module associated with B cell function. This module exhibited a significant correlation with the aggravation of RA during pregnancy and showed significant enrichment of genes that exhibited differential expression between the groups of RA patients who improved and those who worsened. Additionally, an expression signature related to neutrophils was identified in the RA-improved group at the baseline.

A pilot study dataset published in the Journal of Rheumatology by Pathi et al. revealed that pre-pregnancy expression signatures of RA differed between women who subsequently showed improvement or worsening during pregnancy. This finding suggests that there may be inherent genomic differences influencing how pregnancy affects disease activity. Data and blood samples were collected from 11 women with RA and 5 healthy women both before pregnancy (T0) and in the third trimester (T3). The Clinical Disease Activity Index (CDAI) was employed to assess RA disease activity and RNA sequencing profiles were compared between the groups to identify RA-associated gene expression signatures at each time point. Among the 11 women with RA, 6 demonstrated improvements in their condition during T3, while 3 experienced worsening. In the RA-improved group, 73% of genes no longer exhibited RA-associated expression in T3.

The gene expression signatures identified before pregnancy represent potential biomarkers to predict the subsequent improvement and worsening of RA during pregnancy. This has important implications for personalized treatment during pregnancy. Predicting who will improve and who will worsen will help women in their pregnancy planning and will also help to focus treatment during pregnancy only on those women who are predicted to worsen.

According to the current study researchers, this field has not been well-studied, partly due to the difficulty of recruiting women for a pregnancy study before conception. In the future, they plan to conduct a study in a larger cohort of women to validate these findings. Additionally, the researchers are working to unravel the reasons behind the improvement of RA during pregnancy.

References

  1. Wright M, Smed MK, Nelson JL, Olsen J, Hetland ML, Jewell NP, et al. Pre-pregnancy gene expression signatures are associated with subsequent improvement/worsening of rheumatoid arthritis during pregnancy. Arthritis Research & Therapy. 2023 Oct 4;25(1):191
  2. Pathi A, Wright M, Smed MK, Nelson JL, Olsen J, Hetland ML, et al. The rheumatoid arthritis gene expression signature among women who improve or worsen during pregnancy – a pilot study. J Rheumatol. 2021 Jul;48(7):985–91
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