Understanding the mechanism(s) underlying the natural improvement of rheumatoid arthritis during pregnancy can lead to improved and safer therapies for this disease.
An international US–Danish team of scientists, led by Damini Jawaheer, PhD at the UCSF Benioff Children’s Hospital Oakland Research Institute, has identified a possible link between type I interferons and a natural improvement of rheumatoid arthritis (RA) during pregnancy. These findings could have significant implications in the development of safer therapies for RA. This study entitled, “Pregnancy–induced gene expression changes in vivo among women with rheumatoid arthritis: a pilot study,” was published in the journal Arthritis Research & Therapy.

Approximately 50–75% of women with RA experience a natural improvement of RA during pregnancy, while others experience no change or may worsen during pregnancy.

In order to understand the natural changes in RA during pregnancy, Dr. Jawaheer and her collaborative team examined “gene expression” before pregnancy and at the third trimester in a small sample of women who improved or worsened during pregnancy and among healthy women. Gene expression reflects the behavior of genes and what biological changes they may be inducing in the body. Depending on the body’s needs at any point in time, each gene is turned on or off to different extents, producing different amounts of “RNA” which then results in different amounts of protein being produced from that gene. State–of–the–art RNA sequencing technology enabled the researchers to measure “gene expression.” By measuring the amount of RNA produced by each gene before and during pregnancy, the team was able to estimate how “active” each gene was at each point in time, and how its activity changed during that time.

The researchers compared gene expression at the 3rd trimester to that before pregnancy within each group of women (RA improved, RA worsened, healthy) to gain insight about the biological changes brought about in the mother during pregnancy. “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,” says Dr. Jawaheer.

The team then focused on biological changes that occurred by the 3rd trimester among the RA women who improved, and examined how those differed among the women whose conditions worsened. They observed that a small number of genes showed opposite behaviors in these two groups of women during pregnancy (increased expression when RA improved and decreased expression when RA worsened). Of particular interest to the researchers was that expression of this entire cluster of genes was influenced by type I interferons (IFNs). Thus, the results indicated that type I IFNs could have a role in the natural improvement of RA during pregnancy.

In vitro studies as well as studies of animal models of arthritis suggest that type I IFN most likely has a protective role in RA. Unfortunately, translation of the findings from the animal models to treat human RA using IFNbeta therapy has thus far not been successful. Dr. Jawaheer and her team hope to replicate these initial results in a larger sample of their study cohort, to determine if type I IFNs are indeed beneficial in human RA. Dr. Jawaheer and the team plan to continue the research to determine what causes the natural improvement of RA during pregnancy, so that safer therapies for RA can be developed.