# The pregnancy transcriptome in rheumatoid arthritis

> **NIH NIH R01** · CHILDREN'S HOSPITAL & RES CTR AT OAKLAND · 2020 · $651,622

## Abstract

PROJECT SUMMARY
Rheumatoid arthritis (RA) affects 1% of the adult world population, including 1.5 million adults in the U.S., and
contributes significantly to the global burden of disease. There is currently no cure for RA, and available
medications are often associated with risks of toxicity and adverse events. However, pregnancy is known to
have remarkable disease modifying properties on RA, inducing a natural amelioration in 50-75% of patients,
the mechanism(s) of which remain unknown. Our goal in this proposal is to gain an understanding of the
mechanism(s) underlying the natural amelioration of RA during pregnancy so that, in the long-term, novel
therapy can be developed to mimic the beneficial effect of pregnancy on RA outside the context of pregnancy,
to alleviate RA symptoms in both women and men. We hypothesize that the biological processes that lead to
the natural improvement of RA during pregnancy are reflected in pregnancy-induced changes in gene
expression at the systemic level. We previously established a unique prospective pregnancy cohort of RA and
healthy women, with samples collected before, during and after pregnancy for gene expression studies. We
now propose to examine changes in gene expression that occur during pregnancy in RA and healthy women in
a larger sample of this cohort in order to gain an understanding of potential mechanism(s) whereby pregnancy
naturally modulates disease activity in RA. The proposal is divided into 3 aims. In aim 1, a set of candidate
genes with expression patterns that are associated with improvement in RA disease activity will be
investigated. In aim 2, gene expression signatures associated with RA will be examined before pregnancy and
the influence of pregnancy-induced expression changes on the RA signature will be investigated. In aim 3,
pregnancy-induced gene expression patterns in RA and healthy women will be examined to provide insight into
normal biological changes that occur during pregnancy, and how these may be altered in RA. In all 3 aims,
potential epigenetic mechanisms that may be regulating expression during pregnancy will be investigated to
provide insight into the natural amelioration of RA during pregnancy, and into why some women do not
improve during pregnancy, but worsen. The proposed innovative approach includes a) a unique prospective
pregnancy cohort which includes pre-pregnancy as baseline, b) a successful recruitment approach, c) a
powerful longitudinal study design, d) state-of-the-art RNA sequencing technology and bioinformatics methods
to assess gene expression, e) powerful statistical analysis approaches, and f) epigenetic studies to examine
regulation of candidate gene expression. Such investigations using the proposed approach are novel in the
context of both normal and RA pregnancies. There is a high potential that the findings can lead to identification
of novel drug targets for improved RA therapy without side effects of current medications, and novel
biomarkers...

## Key facts

- **NIH application ID:** 10014566
- **Project number:** 5R01AR073111-04
- **Recipient organization:** CHILDREN'S HOSPITAL & RES CTR AT OAKLAND
- **Principal Investigator:** Damini Jawaheer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $651,622
- **Award type:** 5
- **Project period:** 2017-09-20 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10014566

## Citation

> US National Institutes of Health, RePORTER application 10014566, The pregnancy transcriptome in rheumatoid arthritis (5R01AR073111-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10014566. Licensed CC0.

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