Jun 21 2017
An international US-Danish team of scientists, led by Damini Jawaheer, Ph.D. 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 Arthritis Research & Therapy (May 25, 2017 – vol. 19: 104; DOI: 10.1186/s13075-017-1312-2).
Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects 1.5 million adults in the US, and results in significant disability and compromised quality of life for many patients. There is currently no cure for RA; available medications are often associated with serious side effects. Surprisingly though, approximately 50-75% of women with RA experience a natural improvement of RA during pregnancy. Other women with RA experience no change or their condition may worsen during pregnancy. What causes the natural improvement or worsening of RA during pregnancy has remained unknown over the last several decades.
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 (different from the DNA testing which many companies offer as a service) 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.
Although the researchers had a relatively small sample size, these novel findings nevertheless support a beneficial role for type I IFNs in RA, as has been suggested previously. Type I IFNs appear to have conflicting roles in autoimmune disease. While type I IFN activation in lupus is associated with an increase in disease activity, it correlates with an alleviation of symptoms in multiple sclerosis (MS). IFNβ therapy has been successfully used to treat MS patients. 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 IFNβ 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.