Damini Jawaheer, PhD: Biomarkers may Predict Disease Severity in Pregnant Patients with RA

Damini Jawaheer, PhD

Credit: Feinberg School of Medicine

In an interview with HCPLive, Damini Jawaheer, PhD, research associate professor of medicine (rheumatology), discussed her study “Pre-pregnancy Gene Expression Signatures Among Women with Rheumatoid Arthritis May Represent Predictive Biomarkers for Subsequent Improvement or Worsening During Pregnancy,” presented at the American College of Rheumatology’s 2023 Convergence in San Diego, California.¹

What inspired your team to analyze pre-pregnancy gene expression profiles in women with rheumatoid arthritis (RA)?

Pregnancy can induce a natural improvement of RA in 50-75% of women with this incurable disease, while in others, RA can worsen during pregnancy or remain unchanged. Currently, there are no biomarkers to predict who will improve during pregnancy and who will worsen. Further, this field has not been well studied, partly because it is extremely difficult to identify women with RA for a pregnancy study, especially before they get pregnant. We had previously established a unique RA pregnancy cohort in Denmark, with a pre-pregnancy baseline, for gene expression studies on RA improvement during pregnancy. Many of thewomen in our cohort did not wish to take medications during their pregnancy but were concerned that their disease might worsen during the pregnancy if they chose to stop their medications. To address these concerns, we decided to use the pre-pregnancy data from our cohort to determine whether there are gene expression biomarkers at the pre-pregnancy baseline that can predict improvement or worsening during pregnancy.

Can you tell me a bit more about your study design?

We had enrolled women with RA and healthy women into our cohort before pregnancy and followed them through pregnancy to determine who improved and who worsened during pregnancy. We then used blood samples collected from those women before pregnancy, to examine “gene expression,” ie, to what levels different genes were expressed in the blood of the women who subsequently improved or worsened during pregnancy.

What were the key findings?

By examining the levels at which different genes were expressed before pregnancy, we found that some genes related to neutrophils were highly expressed among the women who improved during pregnancy, and some genes related to B cells were highly expressed among women who worsened. These gene expression differences between the 2 groups of women at the pre-pregnancy stage may potentially represent biomarkers that can be used to predict who will improve or worsen during pregnancy.

In your opinion, what is the clinical significance of these results?

Currently, because it is not possible to determine whether a woman will improve or worsen during pregnancy, all women are treated for their RA during pregnancy – including women who might have improved naturally. These women (who would have improved naturally) and their fetuses are thus unnecessarily exposed to medications during pregnancy. Being able to predict before pregnancy who will improve or worsen during pregnancy will help women with RA and their rheumatologists make informed decisions about their treatment during pregnancy. Hence, women predicted to improve, and their fetuses, do not have to be exposed to medications during pregnancy. Also, that will allow treatment during pregnancy to be targeted only to women predicted to worsen.

Were there any strengths or limitations you'd like to highlight?

A major strength of our study was that our pregnancy cohort had RNA samples available for gene expression assays (RNA sequencing), as well as clinical data from the same women both at a pre-pregnancy timepoint and during pregnancy to assess clinical outcome during pregnancy. We are not aware of any other RA pregnancy cohorts with RNA samples and pre-pregnancy data available for such gene expression studies. In terms of limitations, because our patient sample was small, these results are still preliminary until they are replicated in a larger sample.

Does your team plan on doing any further research on this topic?

Yes, we are planning to replicate our findings in a larger sample of our cohort. We also plan to follow up on these results in a new pregnancy cohort, to determine in more detail how these 2 groups of women with RA differ from each other before pregnancy.

Is there anything else you'd like our audience to know?

This work is part of a larger project that our team has been working on. Our goals for this larger project are to elucidate how pregnancy induces a natural improvement of an incurable disease like RA, so that novel improved therapies for RA can be developed, with fewer side effects, to mimic the natural improvement of RA during pregnancy.

References

1. ^{WrightM, Smed M, NelsonL, OlsenJ, et al. Pre-pregnancy Gene Expression Signatures Among Women with Rheumatoid Arthritis May Represent Predictive Biomarkers for Subsequent Improvement or Worsening During Pregnancy. Presented at: American College of Rheumatology Convergence 2023. San Diego, CA. November 10-15, 2023.}