Gene Expression in Pregnant Women with Rheumatoid Arthritis

Type I interferons (IFNs) may play a role in the natural improvement of rheumatoid arthritis (RA) during pregnancy, new findings suggest.

In the United States, an estimated 1.5 million individuals are living with RA. Many pregnant women will find that their symptoms go into remission during pregnancy, whereas others may see their symptoms worsen or experience no change at all.

Little has been understood about the changes in gene expression induced by pregnancy in women with RA and healthy women. This is because few studies have been conducted and the lack of pre-pregnancy samples available at baseline.

In a study published in Arthritis Research & Therapy, investigators hypothesized that there is an overlap between pregnancy-induced changes in gene expression among women with RA who improve during pregnancy and among healthy women, and differ from changes among women with RA who worsen during pregnancy.

RNA sequencing (RNA-seq) generated global gene expression profiles from 11 women with RA and 5 healthy women before pregnancy and at the third trimester.

By the third trimester, 8 pregnant women with RA showed an improvement in disease activity and 3 worsened. The investigators used differential expression analysis to identify genes demonstrating significant changes in expression within each of the RA and healthy groups, in addition to between the groups at each time point.

“Most of the pregnancy-induced biological changes that we observed in both RA groups were also present among healthy women, suggesting that those were most likely normal pregnancy-related changes,” said lead investigator Damini Jawaheer, PhD.

Next, the investigators examined and compared the biological changes that occurred by the third trimester among women with RA who improved with women whose conditions worsened.

The results of the study showed that the expression of a small number of genes differed between the 2 groups of pregnant women. For women who experienced an improvement in RA, the expression increased; however, when RA worsened, the expression decreased.

Most notably, was that the gene cluster was influenced by IFNs, suggesting that type I IFNs may play a role in the natural improvement of RA during pregnancy.

“In 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,” the authors concluded. “These findings warrant a 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.”

The investigators plan to continue their research to determine what causes the natural improvement of RA during pregnancy to help develop safer treatments for patients with RA.