The Rheumatoid Arthritis Gene Expression Signature Among Women Who Improve or Worsen During Pregnancy: A Pilot Study

Abstract

Objective To assess whether gene expression signatures associated with rheumatoid arthritis (RA) before pregnancy differ between women who improve or worsen during pregnancy, and to determine whether these expression signatures are altered during pregnancy when RA improves or worsens. Methods Clinical data and blood samples were collected before pregnancy (T0) and at the third trimester (T3) from 11 women with RA and 5 healthy women. RA disease activity was assessed using the Clinical Disease Activity Index (CDAI). At each timepoint, RA-associated gene expression signatures were identified using differential expression analysis of RNA sequencing profiles between women with RA and healthy women. Results Of the women with RA, 6 improved by T3 (RAimproved), 3 worsened (RAworsened), and 2 were excluded. At T0, mean CDAI scores were similar in both groups (RAimproved 11.2 ± 9.8; RAworsened 13.8 ± 6.7; Wilcoxon rank-sum test: P = 0.6). In the RAimproved group, 89 genes were differentially expressed at T0 (q < 0.05 and fold change ≥ 2) compared to healthy women. When RA improved at T3, 65 of 89 (73%) of these genes no longer displayed RA-associated expression. In the RAworsened group, a largely different RA gene expression signature (429 genes) was identified at T0. When RA disease activity worsened at T3, 207 of 429 (48%) genes lost their differential expression, while an additional 151 genes became newly differentially expressed. Conclusion In our pilot dataset, pre-pregnancy RA expression signatures differed between women who subsequently improved or worsened during pregnancy, suggesting that inherent genomic differences may influence how pregnancy affects disease activity. Further, these RA signatures were altered during pregnancy as disease activity changed.