Type I interferons (IFNs) may play a role in the natural amelioration of rheumatoid arthritis (RA) during pregnancy, a new pilot study suggests.
For women living with RA who become pregnant, little is known about the biology of pregnancy in terms of the overall systemic changes it induces, how they may differ between women with RA and healthy women, and how pregnancy-induced changes may have an impact on RA.
However, it is well documented that pregnancy can produce significant changes in RA disease activity. Between 50% and 75% of women with RA may experience a natural improvement in disease activity while pregnant, whereas other women may worsen or show no change.
Led by Damini Jawaheer, PhD, of the UCSF Benioff Children’s Hospital in Oakland, California, researchers hypothesized that pregnancy-induced changes in gene expressions among women with RA who improve during pregnancy may overlap substantially with those observed among healthy women and may differ from changes among women with RA who worsen during pregnancy.
They reported their findings in Arthritis Research & Therapy.
The study established a cohort of women with RA and healthy women of Danish descent, who were enrolled prior to pregnancy and followed prospectively through pregnancy. Using state-of-the-art RNA sequencing technology, the researchers examined systemic global gene expression in peripheral blood from a subset of 11 women with RA and 5 healthy women as a pilot.
Women with RA fulfilled the 1987 revised American College of Rheumatology criteria for RA. Disease activity was assessed using the Disease Activity Score based on 28 joints and 4 variables (DAS28-CRP4). Change in DAS28 score from pre-pregnancy to the third trimester was calculated, separating the women with RA into 2 subsets. Women with a decrease in DAS28 scores were considered “improved” during pregnancy; those with an increase in DAS28 scores were considered “worsened.” Disease activity categories (remission, low, moderate, or high) were assessed using previously defined criteria.
The researchers performed differential gene expression analysis, which compared normalized gene-level counts between the third trimester and pre-pregnancy time points within each group of women (improved, worsened, and healthy). Comparisons between groups (improved vs worsened and improved vs healthy) also were performed. This analysis allowed for further investigation of pregnancy-induced gene expression patterns and fold-changes within the pilot dataset.
Of the 11 women with RA, 8 fell into the improved group and 3 were in the worsened group. In the improved group, a total of 1296 genes showed significant differential expression between the third trimester and pre-pregnancy time points. Of these, 161 genes displayed 2-fold or more change in expression. A large proportion of the 161 genes were also differentially expressed among healthy women. Some (n=31) were differentially expressed among worsened women.
Goin DE, Smed MK, Pachter L, et al. “Pregnancy-induced gene expressions changes in vivo among women with rheumatoid arthritis: a pilot study.” Arthritis Res Ther. 2017;19:104. doi: 10.1186/s13075-017-1312-2.